Journal of Clinical Outcomes Management

SAN DIEGO – When patients ask if collagen supplements can benefit their skin, what should you tell them?

According to Ava Shamban, MD, a dermatologist who practices in Santa Monica, Calif., limited data exist to suggest that consuming collagen-dense foods can directly benefit skin or joint health. And in her opinion, more research is needed to establish knowledge of the effects and physiologic mechanism of collagen supplementation.

“Collagen is the most abundant protein in the skin; it is found only in animal flesh like meat and fish that contain connective tissue,” she said at the annual Masters of Aesthetics Symposium. “We produce less collagen as we age. External factors can slow down our collagen production, including smoking, sun exposure, lack of sleep/exercise, and alcohol consumption.”

Though human studies are lacking, some trials have found that collagen supplements may improve skin hydration and elasticity. “Maybe there’s some benefit, but the digestive process breaks collagen down into amino acids, so I don’t buy it,” she said.

At the meeting, Dr. Shamban discussed other topics related to the effect of supplements and nutrition on the skin:

Can Nutrafol reverse permanent hair loss? “It definitely doesn’t do that,” she said. “Can it help regrow hair? Perhaps.” Nutrafol is an over-the-counter supplement that aims to relieve moderate hair thinning or strengthen hair to prevent breakage, and is physician-formulated with medical-grade ingredients that target root causes of thinning such as stress, lifestyle, hormones, and nutrition.

As for biotin, “we now know that high levels of biotin can actually cause hair loss,” she said. “If you have advanced hair loss, supplements may not work for you. There is no hair regrowth supplement that can bring back a dead hair follicle. Can it help a miniaturized hair follicle? Maybe. Platelet-rich plasma injections have been shown to stimulate hair growth, but only if the follicle is miniaturized, not if it’s totally gone.”

How does the human microbiome affect skin? In a review of sequencing surveys of healthy adults, “the composition of microbial communities was found to be primarily dependent on the physiology of the skin site, with changes in the relative abundance of bacterial taxa associated with moist, dry, and sebaceous environments,” the authors reported . “The microbiome is the genetic material of all the microbes that live inside the body, including bacteria, fungi, protozoa, and viruses,” Dr. Shamban said. “The more diverse the microbiota is, the healthier it’s considered. That diversity is enriched through a diet full of various vegetables and fruits.”

Nearly all adults are colonized with Cutibacterium acnes (formerly Propionibacterium acnes), but only a minority have acne, which highlights the importance of studying diseases in the broader context of host genetics, immune or barrier defects, the microbiome, and the environment, she added. For example, the decreased diversity of the skin microbiome in people with atopic dermatitis has been linked to a reduction in environmental biodiversity in the areas surrounding their homes.

Do adaptogens have a role in skin care? Adaptogens such as ashwagandha, elderberry, ginseng, licorice root, neem, moringa, and reishi mushrooms have been used in Chinese and Ayurvedic medicine for centuries and are purported to promote adaptability, resilience, and survival of living organisms in stress. They appear to affect the neuroendocrine immune system and at low doses may function as mild stress mimetics.

“The idea is that combining adaptogens into skin care can reinforce and support the skin’s resistance against stressors that can accelerate visible signs of aging,” said Dr. Shamban. “They share some similarities with antioxidants in that their main purpose is to protect the body from external stressors such as UV rays, oxidation, and pollution.” More studies should be conducted to verify effectiveness, she said, “but Eastern practices that have incorporated it for centuries shouldn’t be fully dismissed. Most doctors believe adaptogens are safe, but how they interact with the mechanics of the body’s stress response system remains a mystery.”

Embrace the consumption of micronutrients. Inspired by work from dermatologist Zoe Diana Draelos, MD, Dr. Shamban advises patients to eat a “rainbow of different colored foods” every day, especially those rich in vitamins A, C, and E. Green foods are generally rich in vitamin E, brown foods are rich in trace minerals, and blue/purple foods are rich in antioxidants. “It’s always best to get nutrients from a rich, healthy diet, but sometimes our skin requires extra help,” she said.

A randomized, placebo-controlled, double-blind study by French researchers, which showed that skin is prone to seasonal changes during the winter, particularly in exposed areas, also looked at whether a daily micronutrient supplement with ingredients that included green tea extract, blackcurrant seed oil, and magnesium, had an impact on the negative effects of winter weather on the skin. “The data indicate that oral micronutrient supplementation can be a safe treatment, with no serious side effects, and may prevent or even eliminate the negative effects of winter on the skin,” she said.

Dr. Shamban disclosed that she conducts clinical trials for many pharmaceutical and device companies.

SAN DIEGO – When patients ask if collagen supplements can benefit their skin, what should you tell them?

According to Ava Shamban, MD, a dermatologist who practices in Santa Monica, Calif., limited data exist to suggest that consuming collagen-dense foods can directly benefit skin or joint health. And in her opinion, more research is needed to establish knowledge of the effects and physiologic mechanism of collagen supplementation.

“Collagen is the most abundant protein in the skin; it is found only in animal flesh like meat and fish that contain connective tissue,” she said at the annual Masters of Aesthetics Symposium. “We produce less collagen as we age. External factors can slow down our collagen production, including smoking, sun exposure, lack of sleep/exercise, and alcohol consumption.”

Though human studies are lacking, some trials have found that collagen supplements may improve skin hydration and elasticity. “Maybe there’s some benefit, but the digestive process breaks collagen down into amino acids, so I don’t buy it,” she said.

At the meeting, Dr. Shamban discussed other topics related to the effect of supplements and nutrition on the skin:

Can Nutrafol reverse permanent hair loss? “It definitely doesn’t do that,” she said. “Can it help regrow hair? Perhaps.” Nutrafol is an over-the-counter supplement that aims to relieve moderate hair thinning or strengthen hair to prevent breakage, and is physician-formulated with medical-grade ingredients that target root causes of thinning such as stress, lifestyle, hormones, and nutrition.

As for biotin, “we now know that high levels of biotin can actually cause hair loss,” she said. “If you have advanced hair loss, supplements may not work for you. There is no hair regrowth supplement that can bring back a dead hair follicle. Can it help a miniaturized hair follicle? Maybe. Platelet-rich plasma injections have been shown to stimulate hair growth, but only if the follicle is miniaturized, not if it’s totally gone.”

How does the human microbiome affect skin? In a review of sequencing surveys of healthy adults, “the composition of microbial communities was found to be primarily dependent on the physiology of the skin site, with changes in the relative abundance of bacterial taxa associated with moist, dry, and sebaceous environments,” the authors reported . “The microbiome is the genetic material of all the microbes that live inside the body, including bacteria, fungi, protozoa, and viruses,” Dr. Shamban said. “The more diverse the microbiota is, the healthier it’s considered. That diversity is enriched through a diet full of various vegetables and fruits.”

Nearly all adults are colonized with Cutibacterium acnes (formerly Propionibacterium acnes), but only a minority have acne, which highlights the importance of studying diseases in the broader context of host genetics, immune or barrier defects, the microbiome, and the environment, she added. For example, the decreased diversity of the skin microbiome in people with atopic dermatitis has been linked to a reduction in environmental biodiversity in the areas surrounding their homes.

Do adaptogens have a role in skin care? Adaptogens such as ashwagandha, elderberry, ginseng, licorice root, neem, moringa, and reishi mushrooms have been used in Chinese and Ayurvedic medicine for centuries and are purported to promote adaptability, resilience, and survival of living organisms in stress. They appear to affect the neuroendocrine immune system and at low doses may function as mild stress mimetics.

“The idea is that combining adaptogens into skin care can reinforce and support the skin’s resistance against stressors that can accelerate visible signs of aging,” said Dr. Shamban. “They share some similarities with antioxidants in that their main purpose is to protect the body from external stressors such as UV rays, oxidation, and pollution.” More studies should be conducted to verify effectiveness, she said, “but Eastern practices that have incorporated it for centuries shouldn’t be fully dismissed. Most doctors believe adaptogens are safe, but how they interact with the mechanics of the body’s stress response system remains a mystery.”

Embrace the consumption of micronutrients. Inspired by work from dermatologist Zoe Diana Draelos, MD, Dr. Shamban advises patients to eat a “rainbow of different colored foods” every day, especially those rich in vitamins A, C, and E. Green foods are generally rich in vitamin E, brown foods are rich in trace minerals, and blue/purple foods are rich in antioxidants. “It’s always best to get nutrients from a rich, healthy diet, but sometimes our skin requires extra help,” she said.

A randomized, placebo-controlled, double-blind study by French researchers, which showed that skin is prone to seasonal changes during the winter, particularly in exposed areas, also looked at whether a daily micronutrient supplement with ingredients that included green tea extract, blackcurrant seed oil, and magnesium, had an impact on the negative effects of winter weather on the skin. “The data indicate that oral micronutrient supplementation can be a safe treatment, with no serious side effects, and may prevent or even eliminate the negative effects of winter on the skin,” she said.

Dr. Shamban disclosed that she conducts clinical trials for many pharmaceutical and device companies.

SAN DIEGO – When patients ask if collagen supplements can benefit their skin, what should you tell them?

According to Ava Shamban, MD, a dermatologist who practices in Santa Monica, Calif., limited data exist to suggest that consuming collagen-dense foods can directly benefit skin or joint health. And in her opinion, more research is needed to establish knowledge of the effects and physiologic mechanism of collagen supplementation.

“Collagen is the most abundant protein in the skin; it is found only in animal flesh like meat and fish that contain connective tissue,” she said at the annual Masters of Aesthetics Symposium. “We produce less collagen as we age. External factors can slow down our collagen production, including smoking, sun exposure, lack of sleep/exercise, and alcohol consumption.”

Though human studies are lacking, some trials have found that collagen supplements may improve skin hydration and elasticity. “Maybe there’s some benefit, but the digestive process breaks collagen down into amino acids, so I don’t buy it,” she said.

At the meeting, Dr. Shamban discussed other topics related to the effect of supplements and nutrition on the skin:

Can Nutrafol reverse permanent hair loss? “It definitely doesn’t do that,” she said. “Can it help regrow hair? Perhaps.” Nutrafol is an over-the-counter supplement that aims to relieve moderate hair thinning or strengthen hair to prevent breakage, and is physician-formulated with medical-grade ingredients that target root causes of thinning such as stress, lifestyle, hormones, and nutrition.

As for biotin, “we now know that high levels of biotin can actually cause hair loss,” she said. “If you have advanced hair loss, supplements may not work for you. There is no hair regrowth supplement that can bring back a dead hair follicle. Can it help a miniaturized hair follicle? Maybe. Platelet-rich plasma injections have been shown to stimulate hair growth, but only if the follicle is miniaturized, not if it’s totally gone.”

How does the human microbiome affect skin? In a review of sequencing surveys of healthy adults, “the composition of microbial communities was found to be primarily dependent on the physiology of the skin site, with changes in the relative abundance of bacterial taxa associated with moist, dry, and sebaceous environments,” the authors reported . “The microbiome is the genetic material of all the microbes that live inside the body, including bacteria, fungi, protozoa, and viruses,” Dr. Shamban said. “The more diverse the microbiota is, the healthier it’s considered. That diversity is enriched through a diet full of various vegetables and fruits.”

Nearly all adults are colonized with Cutibacterium acnes (formerly Propionibacterium acnes), but only a minority have acne, which highlights the importance of studying diseases in the broader context of host genetics, immune or barrier defects, the microbiome, and the environment, she added. For example, the decreased diversity of the skin microbiome in people with atopic dermatitis has been linked to a reduction in environmental biodiversity in the areas surrounding their homes.

Do adaptogens have a role in skin care? Adaptogens such as ashwagandha, elderberry, ginseng, licorice root, neem, moringa, and reishi mushrooms have been used in Chinese and Ayurvedic medicine for centuries and are purported to promote adaptability, resilience, and survival of living organisms in stress. They appear to affect the neuroendocrine immune system and at low doses may function as mild stress mimetics.

“The idea is that combining adaptogens into skin care can reinforce and support the skin’s resistance against stressors that can accelerate visible signs of aging,” said Dr. Shamban. “They share some similarities with antioxidants in that their main purpose is to protect the body from external stressors such as UV rays, oxidation, and pollution.” More studies should be conducted to verify effectiveness, she said, “but Eastern practices that have incorporated it for centuries shouldn’t be fully dismissed. Most doctors believe adaptogens are safe, but how they interact with the mechanics of the body’s stress response system remains a mystery.”

Embrace the consumption of micronutrients. Inspired by work from dermatologist Zoe Diana Draelos, MD, Dr. Shamban advises patients to eat a “rainbow of different colored foods” every day, especially those rich in vitamins A, C, and E. Green foods are generally rich in vitamin E, brown foods are rich in trace minerals, and blue/purple foods are rich in antioxidants. “It’s always best to get nutrients from a rich, healthy diet, but sometimes our skin requires extra help,” she said.

A randomized, placebo-controlled, double-blind study by French researchers, which showed that skin is prone to seasonal changes during the winter, particularly in exposed areas, also looked at whether a daily micronutrient supplement with ingredients that included green tea extract, blackcurrant seed oil, and magnesium, had an impact on the negative effects of winter weather on the skin. “The data indicate that oral micronutrient supplementation can be a safe treatment, with no serious side effects, and may prevent or even eliminate the negative effects of winter on the skin,” she said.

Dr. Shamban disclosed that she conducts clinical trials for many pharmaceutical and device companies.

The U.S. Food and Drug Administration has approved the anti–amyloid-beta protofibril antibody lecanemab (Leqembi, Eisai) for the treatment of early Alzheimer’s disease.

Like its controversial cousin aducanumab (Aduhelm, Biogen/Eisai), lecanemab was approved under the FDA’s accelerated approval pathway, which can be used to fast-track a drug that provides a meaningful therapeutic advantage over existing treatments for a serious or life-threatening illness.

Unlike aducanumab, however, there was no formal FDA advisory committee meeting on lecanemab prior to approval.

“Alzheimer’s disease immeasurably incapacitates the lives of those who suffer from it and has devastating effects on their loved ones,” Billy Dunn, MD, director of the Office of Neuroscience in the FDA’s Center for Drug Evaluation and Research, said in a press release.

“This treatment option is the latest therapy to target and affect the underlying disease process of Alzheimer’s, instead of only treating the symptoms of the disease,” Dr. Dunn added.

Eisai has reported that lecanemab will cost $26,500 a year.

Modest benefit, adverse events

The FDA noted, “The labeling states that treatment with Leqembi should be initiated in patients with mild cognitive impairment or mild dementia stage of disease, the population in which treatment was studied in clinical trials.”

The agency approved the treatment on the basis of findings from the CLARITY AD trial, which showed modest cognitive benefit for patients with early AD – but at a cost of increased risk for amyloid-related edema and effusions.

The trial enrolled 1,795 adults with mild cognitive impairment or early Alzheimer’s disease in whom amyloid pathology in the brain had been confirmed. Treatment consisted of lecanemab 10 mg/kg biweekly or matching placebo.

After 18 months of treatment, lecanemab slowed cognitive decline by 27%, compared with placebo, as measured by the Clinical Dementia Rating–Sum of Boxes (CDR-SB). This was an absolute difference of 0.45 points (change from baseline, 1.21 for lecanemab vs. 1.66 with placebo; P < .001).

While the results are “welcome news,” a 0.45-point difference on the CDR-SB might not be clinically meaningful, authors of a recent editorial in The Lancet cautioned.

Amyloid-related imaging abnormalities that manifest as edema or microhemorrhages also occurred in one in five patients taking lecanemab.

In addition, a newly published case report in The New England Journal of Medicine describes a patient with Alzheimer’s disease who was taking lecanemab and who died after experiencing numerous intracerebral hemorrhages during treatment with tissue plasminogen activator (tPA) for acute ischemic stroke.

“The findings raise the possibility of cerebral hemorrhages and necrotizing vasculopathy associated with tPA infusion in a patient with cerebrovascular amyloid who had received lecanemab,” the authors wrote.
 

Alzheimer’s Association reaction

Still, in anticipation of accelerated approval of lecanemab and the antiamyloid drug donanemab (Eli Lilly), which the FDA has also fast-tracked, the Alzheimer’s Association filed a formal request last month with the Centers for Medicare & Medicaid Services asking that it provide full and unrestricted coverage for FDA-approved Alzheimer’s disease treatments.

In a letter addressed to CMS administrator Chiquita Brooks-LaSure, the association asked the agency to remove the requirements for “coverage with evidence development” in its national coverage determination for FDA-approved antiamyloid monoclonal antibodies.

“Each day matters when it comes to slowing the progression of this disease,” Joanne Pike, DrPH, president and CEO for the Alzheimer’s Association, noted in a news release at the time.

“The current CMS policy to severely limit access to these treatments eliminates people’s options, is resulting in continued irreversible disease progression, and contributes to greater health inequities. That’s not acceptable,” Dr. Pike added.

After news of today’s approval was released, Dr. Pike noted in a new release, “The Alzheimer’s Association welcomes and celebrates this action by the FDA. We now have a second approved treatment that changes the course of Alzheimer’s disease in a meaningful way for people in the early stages of the disease.”

Maria C. Carrillo, PhD, chief science officer at the Alzheimer’s Association, called today’s approval “a milestone achievement.”

“The progress we’ve seen in not only this class of treatments but also in the diversification of treatment types and targets over the past few years is exciting and provides real hope to those impacted by this devastating disease,” Dr. Carrillo said.
 

Critical issues

Commenting on the approval, Alvaro Pascual-Leone, MD, PhD, professor of neurology at Harvard Medical School, Boston, and chief medical officer at Linus Health, said FDA approval of lecanemab and its adoption in the clinic represent a “very exciting development and prospect; but arguably some critical issues need to be considered.”

He noted that the health care system “is not currently prepared to cope with the challenges and demands of lecanemab,” as well as future pharmacologic agents.

“First, we need better workflows to identify suitable patients who can most benefit from this treatment,” said Dr. Pascual-Leone. He added that beyond identification of cognitive difficulties, amyloid status will need to be determined.

“Presently, this requires expensive and invasive tests,” such as positron-emission tomography scans or lumbar punctures for cerebrospinal fluid analysis. However, these are not fully covered by insurance companies and would be challenging to fully scale, he noted.

“In addition to screening, health systems will need to resolve the logistics challenges around the administration of lecanemab with twice-monthly infusions and the need for careful longitudinal evaluations for potential side effects,” said Dr. Pascual-Leone.

“While lecanemab may represent the first disease-modifying therapy widely available for early Alzheimer’s disease, the likely more promising approach is the addition of other therapies to lecanemab as part of a multi-intervention strategy combining pharmacologic and nonpharmacologic interventions,” he added.

Dr. Pascual-Leone has served as a paid member on scientific advisory boards for Neuroelectrics, Magstim, TetraNeuron, Skin2Neuron, MedRhythms, and Hearts Radiant and is a cofounder of TI Solutions and Linus Health.

A version of this article first appeared on Medscape.com.

This article was updated 1/9/23.

The U.S. Food and Drug Administration has approved the anti–amyloid-beta protofibril antibody lecanemab (Leqembi, Eisai) for the treatment of early Alzheimer’s disease.

Like its controversial cousin aducanumab (Aduhelm, Biogen/Eisai), lecanemab was approved under the FDA’s accelerated approval pathway, which can be used to fast-track a drug that provides a meaningful therapeutic advantage over existing treatments for a serious or life-threatening illness.

Unlike aducanumab, however, there was no formal FDA advisory committee meeting on lecanemab prior to approval.

“Alzheimer’s disease immeasurably incapacitates the lives of those who suffer from it and has devastating effects on their loved ones,” Billy Dunn, MD, director of the Office of Neuroscience in the FDA’s Center for Drug Evaluation and Research, said in a press release.

“This treatment option is the latest therapy to target and affect the underlying disease process of Alzheimer’s, instead of only treating the symptoms of the disease,” Dr. Dunn added.

Eisai has reported that lecanemab will cost $26,500 a year.

Modest benefit, adverse events

The FDA noted, “The labeling states that treatment with Leqembi should be initiated in patients with mild cognitive impairment or mild dementia stage of disease, the population in which treatment was studied in clinical trials.”

The agency approved the treatment on the basis of findings from the CLARITY AD trial, which showed modest cognitive benefit for patients with early AD – but at a cost of increased risk for amyloid-related edema and effusions.

The trial enrolled 1,795 adults with mild cognitive impairment or early Alzheimer’s disease in whom amyloid pathology in the brain had been confirmed. Treatment consisted of lecanemab 10 mg/kg biweekly or matching placebo.

After 18 months of treatment, lecanemab slowed cognitive decline by 27%, compared with placebo, as measured by the Clinical Dementia Rating–Sum of Boxes (CDR-SB). This was an absolute difference of 0.45 points (change from baseline, 1.21 for lecanemab vs. 1.66 with placebo; P < .001).

While the results are “welcome news,” a 0.45-point difference on the CDR-SB might not be clinically meaningful, authors of a recent editorial in The Lancet cautioned.

Amyloid-related imaging abnormalities that manifest as edema or microhemorrhages also occurred in one in five patients taking lecanemab.

In addition, a newly published case report in The New England Journal of Medicine describes a patient with Alzheimer’s disease who was taking lecanemab and who died after experiencing numerous intracerebral hemorrhages during treatment with tissue plasminogen activator (tPA) for acute ischemic stroke.

“The findings raise the possibility of cerebral hemorrhages and necrotizing vasculopathy associated with tPA infusion in a patient with cerebrovascular amyloid who had received lecanemab,” the authors wrote.
 

Alzheimer’s Association reaction

Still, in anticipation of accelerated approval of lecanemab and the antiamyloid drug donanemab (Eli Lilly), which the FDA has also fast-tracked, the Alzheimer’s Association filed a formal request last month with the Centers for Medicare & Medicaid Services asking that it provide full and unrestricted coverage for FDA-approved Alzheimer’s disease treatments.

In a letter addressed to CMS administrator Chiquita Brooks-LaSure, the association asked the agency to remove the requirements for “coverage with evidence development” in its national coverage determination for FDA-approved antiamyloid monoclonal antibodies.

“Each day matters when it comes to slowing the progression of this disease,” Joanne Pike, DrPH, president and CEO for the Alzheimer’s Association, noted in a news release at the time.

“The current CMS policy to severely limit access to these treatments eliminates people’s options, is resulting in continued irreversible disease progression, and contributes to greater health inequities. That’s not acceptable,” Dr. Pike added.

After news of today’s approval was released, Dr. Pike noted in a new release, “The Alzheimer’s Association welcomes and celebrates this action by the FDA. We now have a second approved treatment that changes the course of Alzheimer’s disease in a meaningful way for people in the early stages of the disease.”

Maria C. Carrillo, PhD, chief science officer at the Alzheimer’s Association, called today’s approval “a milestone achievement.”

“The progress we’ve seen in not only this class of treatments but also in the diversification of treatment types and targets over the past few years is exciting and provides real hope to those impacted by this devastating disease,” Dr. Carrillo said.
 

Critical issues

Commenting on the approval, Alvaro Pascual-Leone, MD, PhD, professor of neurology at Harvard Medical School, Boston, and chief medical officer at Linus Health, said FDA approval of lecanemab and its adoption in the clinic represent a “very exciting development and prospect; but arguably some critical issues need to be considered.”

He noted that the health care system “is not currently prepared to cope with the challenges and demands of lecanemab,” as well as future pharmacologic agents.

“First, we need better workflows to identify suitable patients who can most benefit from this treatment,” said Dr. Pascual-Leone. He added that beyond identification of cognitive difficulties, amyloid status will need to be determined.

“Presently, this requires expensive and invasive tests,” such as positron-emission tomography scans or lumbar punctures for cerebrospinal fluid analysis. However, these are not fully covered by insurance companies and would be challenging to fully scale, he noted.

“In addition to screening, health systems will need to resolve the logistics challenges around the administration of lecanemab with twice-monthly infusions and the need for careful longitudinal evaluations for potential side effects,” said Dr. Pascual-Leone.

“While lecanemab may represent the first disease-modifying therapy widely available for early Alzheimer’s disease, the likely more promising approach is the addition of other therapies to lecanemab as part of a multi-intervention strategy combining pharmacologic and nonpharmacologic interventions,” he added.

Dr. Pascual-Leone has served as a paid member on scientific advisory boards for Neuroelectrics, Magstim, TetraNeuron, Skin2Neuron, MedRhythms, and Hearts Radiant and is a cofounder of TI Solutions and Linus Health.

A version of this article first appeared on Medscape.com.

This article was updated 1/9/23.

The U.S. Food and Drug Administration has approved the anti–amyloid-beta protofibril antibody lecanemab (Leqembi, Eisai) for the treatment of early Alzheimer’s disease.

Like its controversial cousin aducanumab (Aduhelm, Biogen/Eisai), lecanemab was approved under the FDA’s accelerated approval pathway, which can be used to fast-track a drug that provides a meaningful therapeutic advantage over existing treatments for a serious or life-threatening illness.

Unlike aducanumab, however, there was no formal FDA advisory committee meeting on lecanemab prior to approval.

“Alzheimer’s disease immeasurably incapacitates the lives of those who suffer from it and has devastating effects on their loved ones,” Billy Dunn, MD, director of the Office of Neuroscience in the FDA’s Center for Drug Evaluation and Research, said in a press release.

“This treatment option is the latest therapy to target and affect the underlying disease process of Alzheimer’s, instead of only treating the symptoms of the disease,” Dr. Dunn added.

Eisai has reported that lecanemab will cost $26,500 a year.

Modest benefit, adverse events

The FDA noted, “The labeling states that treatment with Leqembi should be initiated in patients with mild cognitive impairment or mild dementia stage of disease, the population in which treatment was studied in clinical trials.”

The agency approved the treatment on the basis of findings from the CLARITY AD trial, which showed modest cognitive benefit for patients with early AD – but at a cost of increased risk for amyloid-related edema and effusions.

The trial enrolled 1,795 adults with mild cognitive impairment or early Alzheimer’s disease in whom amyloid pathology in the brain had been confirmed. Treatment consisted of lecanemab 10 mg/kg biweekly or matching placebo.

After 18 months of treatment, lecanemab slowed cognitive decline by 27%, compared with placebo, as measured by the Clinical Dementia Rating–Sum of Boxes (CDR-SB). This was an absolute difference of 0.45 points (change from baseline, 1.21 for lecanemab vs. 1.66 with placebo; P < .001).

While the results are “welcome news,” a 0.45-point difference on the CDR-SB might not be clinically meaningful, authors of a recent editorial in The Lancet cautioned.

Amyloid-related imaging abnormalities that manifest as edema or microhemorrhages also occurred in one in five patients taking lecanemab.

In addition, a newly published case report in The New England Journal of Medicine describes a patient with Alzheimer’s disease who was taking lecanemab and who died after experiencing numerous intracerebral hemorrhages during treatment with tissue plasminogen activator (tPA) for acute ischemic stroke.

“The findings raise the possibility of cerebral hemorrhages and necrotizing vasculopathy associated with tPA infusion in a patient with cerebrovascular amyloid who had received lecanemab,” the authors wrote.
 

Alzheimer’s Association reaction

Still, in anticipation of accelerated approval of lecanemab and the antiamyloid drug donanemab (Eli Lilly), which the FDA has also fast-tracked, the Alzheimer’s Association filed a formal request last month with the Centers for Medicare & Medicaid Services asking that it provide full and unrestricted coverage for FDA-approved Alzheimer’s disease treatments.

In a letter addressed to CMS administrator Chiquita Brooks-LaSure, the association asked the agency to remove the requirements for “coverage with evidence development” in its national coverage determination for FDA-approved antiamyloid monoclonal antibodies.

“Each day matters when it comes to slowing the progression of this disease,” Joanne Pike, DrPH, president and CEO for the Alzheimer’s Association, noted in a news release at the time.

“The current CMS policy to severely limit access to these treatments eliminates people’s options, is resulting in continued irreversible disease progression, and contributes to greater health inequities. That’s not acceptable,” Dr. Pike added.

After news of today’s approval was released, Dr. Pike noted in a new release, “The Alzheimer’s Association welcomes and celebrates this action by the FDA. We now have a second approved treatment that changes the course of Alzheimer’s disease in a meaningful way for people in the early stages of the disease.”

Maria C. Carrillo, PhD, chief science officer at the Alzheimer’s Association, called today’s approval “a milestone achievement.”

“The progress we’ve seen in not only this class of treatments but also in the diversification of treatment types and targets over the past few years is exciting and provides real hope to those impacted by this devastating disease,” Dr. Carrillo said.
 

Critical issues

Commenting on the approval, Alvaro Pascual-Leone, MD, PhD, professor of neurology at Harvard Medical School, Boston, and chief medical officer at Linus Health, said FDA approval of lecanemab and its adoption in the clinic represent a “very exciting development and prospect; but arguably some critical issues need to be considered.”

He noted that the health care system “is not currently prepared to cope with the challenges and demands of lecanemab,” as well as future pharmacologic agents.

“First, we need better workflows to identify suitable patients who can most benefit from this treatment,” said Dr. Pascual-Leone. He added that beyond identification of cognitive difficulties, amyloid status will need to be determined.

“Presently, this requires expensive and invasive tests,” such as positron-emission tomography scans or lumbar punctures for cerebrospinal fluid analysis. However, these are not fully covered by insurance companies and would be challenging to fully scale, he noted.

“In addition to screening, health systems will need to resolve the logistics challenges around the administration of lecanemab with twice-monthly infusions and the need for careful longitudinal evaluations for potential side effects,” said Dr. Pascual-Leone.

“While lecanemab may represent the first disease-modifying therapy widely available for early Alzheimer’s disease, the likely more promising approach is the addition of other therapies to lecanemab as part of a multi-intervention strategy combining pharmacologic and nonpharmacologic interventions,” he added.

Dr. Pascual-Leone has served as a paid member on scientific advisory boards for Neuroelectrics, Magstim, TetraNeuron, Skin2Neuron, MedRhythms, and Hearts Radiant and is a cofounder of TI Solutions and Linus Health.

A version of this article first appeared on Medscape.com.

This article was updated 1/9/23.

Medicare beneficiaries will pay no more than $35 a month for insulin in 2023, while ongoing work will be needed to ensure that everyone in the United States with diabetes who needs insulin can afford it.

As of Jan. 1, 2023, the new provision tucked into the Inflation Reduction Act, signed into law by President Biden in August 2022, means that beneficiaries who take insulin via pen or syringe, covered under Medicare part D (prescription drugs), fall under the $35/month co-pay cap.

On July 1, 2023, the same out-of-pocket limit will also apply to those who take insulin via pump, which falls under Medicare part B (durable medical equipment).  

The bill originally included the co-pay cap for people with private insurance as well, but that was stripped out as part of the reconciliation process and didn’t garner the necessary 60 Senate votes to keep it in prior to passage.  

However, since 2019, 22 U.S. states have passed their own co-pay caps for people with state-regulated private insurance, ranging from $25 to $100 for a 30-day supply. A few states also cap the cost of diabetes devices as well.

Moreover, federal legislation could still address co-pay caps for people with private insurance, as well as include provisions to help those without insurance to afford insulin, Niels Knutson, director of government relations for the type 1 diabetes advocacy organization JDRF, told this news organization.

“There’s a whole menu of ideas on how to address the issue of insulin affordability. Most pathways to solving this on the federal level will require 60 votes in the Senate. There is universal recognition that this is a problem. The challenge becomes: is everybody on the same page for how to fix it,” Mr. Knutson said.

JDRF is supporting the bipartisan Improving Needed Safeguards for Users of Lifesaving Insulin Now (INSULIN) Act, introduced in June 2022 by U.S. Senators Jeanne Shaheen (D-NH) and Susan Collins (R-ME), who co-chair the Senate Diabetes Caucus. The bill includes a co-pay cap and also provisions to encourage insulin manufacturers to reduce their list prices.

“The bill is unique in that it adds a pathway to reduce the cost of insulin for everybody, regardless of whether they have insurance or not ... We see the Insulin Act as being the best path forward and the most viable path to have the biggest impact for the most people,” Mr. Knutson explained.

At the same time, JDRF is also supporting a nonprofit pharmaceutical company called Civica, which plans to bring biosimilar versions of the insulin analogs glargine, lispro, and aspart to the U.S. market by 2024 at a cost of no more than $30 for a vial and $50 for a box of prefilled pens. The state of California is expected to partner with Civica as well.

“This is just another access point for insulin, especially for folks who are uninsured, that would make a big impact,” Mr. Knutson said.

Other entities that have announced intentions to bring lower-cost insulin to the United States market include the Korean firm Undbio and billionaire entrepreneur Mark Cuban, through his company Cost Plus Drugs.

“Insulin is such a clear and present crisis that we need to address,” Mr. Knutson said. “You’re seeing this problem being recognized and solutions from all different angles coming at it.”

A version of this article first appeared on Medscape.com.

Medicare beneficiaries will pay no more than $35 a month for insulin in 2023, while ongoing work will be needed to ensure that everyone in the United States with diabetes who needs insulin can afford it.

As of Jan. 1, 2023, the new provision tucked into the Inflation Reduction Act, signed into law by President Biden in August 2022, means that beneficiaries who take insulin via pen or syringe, covered under Medicare part D (prescription drugs), fall under the $35/month co-pay cap.

On July 1, 2023, the same out-of-pocket limit will also apply to those who take insulin via pump, which falls under Medicare part B (durable medical equipment).  

The bill originally included the co-pay cap for people with private insurance as well, but that was stripped out as part of the reconciliation process and didn’t garner the necessary 60 Senate votes to keep it in prior to passage.  

However, since 2019, 22 U.S. states have passed their own co-pay caps for people with state-regulated private insurance, ranging from $25 to $100 for a 30-day supply. A few states also cap the cost of diabetes devices as well.

Moreover, federal legislation could still address co-pay caps for people with private insurance, as well as include provisions to help those without insurance to afford insulin, Niels Knutson, director of government relations for the type 1 diabetes advocacy organization JDRF, told this news organization.

“There’s a whole menu of ideas on how to address the issue of insulin affordability. Most pathways to solving this on the federal level will require 60 votes in the Senate. There is universal recognition that this is a problem. The challenge becomes: is everybody on the same page for how to fix it,” Mr. Knutson said.

JDRF is supporting the bipartisan Improving Needed Safeguards for Users of Lifesaving Insulin Now (INSULIN) Act, introduced in June 2022 by U.S. Senators Jeanne Shaheen (D-NH) and Susan Collins (R-ME), who co-chair the Senate Diabetes Caucus. The bill includes a co-pay cap and also provisions to encourage insulin manufacturers to reduce their list prices.

“The bill is unique in that it adds a pathway to reduce the cost of insulin for everybody, regardless of whether they have insurance or not ... We see the Insulin Act as being the best path forward and the most viable path to have the biggest impact for the most people,” Mr. Knutson explained.

At the same time, JDRF is also supporting a nonprofit pharmaceutical company called Civica, which plans to bring biosimilar versions of the insulin analogs glargine, lispro, and aspart to the U.S. market by 2024 at a cost of no more than $30 for a vial and $50 for a box of prefilled pens. The state of California is expected to partner with Civica as well.

“This is just another access point for insulin, especially for folks who are uninsured, that would make a big impact,” Mr. Knutson said.

Other entities that have announced intentions to bring lower-cost insulin to the United States market include the Korean firm Undbio and billionaire entrepreneur Mark Cuban, through his company Cost Plus Drugs.

“Insulin is such a clear and present crisis that we need to address,” Mr. Knutson said. “You’re seeing this problem being recognized and solutions from all different angles coming at it.”

A version of this article first appeared on Medscape.com.

Medicare beneficiaries will pay no more than $35 a month for insulin in 2023, while ongoing work will be needed to ensure that everyone in the United States with diabetes who needs insulin can afford it.

As of Jan. 1, 2023, the new provision tucked into the Inflation Reduction Act, signed into law by President Biden in August 2022, means that beneficiaries who take insulin via pen or syringe, covered under Medicare part D (prescription drugs), fall under the $35/month co-pay cap.

On July 1, 2023, the same out-of-pocket limit will also apply to those who take insulin via pump, which falls under Medicare part B (durable medical equipment).  

The bill originally included the co-pay cap for people with private insurance as well, but that was stripped out as part of the reconciliation process and didn’t garner the necessary 60 Senate votes to keep it in prior to passage.  

However, since 2019, 22 U.S. states have passed their own co-pay caps for people with state-regulated private insurance, ranging from $25 to $100 for a 30-day supply. A few states also cap the cost of diabetes devices as well.

Moreover, federal legislation could still address co-pay caps for people with private insurance, as well as include provisions to help those without insurance to afford insulin, Niels Knutson, director of government relations for the type 1 diabetes advocacy organization JDRF, told this news organization.

“There’s a whole menu of ideas on how to address the issue of insulin affordability. Most pathways to solving this on the federal level will require 60 votes in the Senate. There is universal recognition that this is a problem. The challenge becomes: is everybody on the same page for how to fix it,” Mr. Knutson said.

JDRF is supporting the bipartisan Improving Needed Safeguards for Users of Lifesaving Insulin Now (INSULIN) Act, introduced in June 2022 by U.S. Senators Jeanne Shaheen (D-NH) and Susan Collins (R-ME), who co-chair the Senate Diabetes Caucus. The bill includes a co-pay cap and also provisions to encourage insulin manufacturers to reduce their list prices.

“The bill is unique in that it adds a pathway to reduce the cost of insulin for everybody, regardless of whether they have insurance or not ... We see the Insulin Act as being the best path forward and the most viable path to have the biggest impact for the most people,” Mr. Knutson explained.

At the same time, JDRF is also supporting a nonprofit pharmaceutical company called Civica, which plans to bring biosimilar versions of the insulin analogs glargine, lispro, and aspart to the U.S. market by 2024 at a cost of no more than $30 for a vial and $50 for a box of prefilled pens. The state of California is expected to partner with Civica as well.

“This is just another access point for insulin, especially for folks who are uninsured, that would make a big impact,” Mr. Knutson said.

Other entities that have announced intentions to bring lower-cost insulin to the United States market include the Korean firm Undbio and billionaire entrepreneur Mark Cuban, through his company Cost Plus Drugs.

“Insulin is such a clear and present crisis that we need to address,” Mr. Knutson said. “You’re seeing this problem being recognized and solutions from all different angles coming at it.”

A version of this article first appeared on Medscape.com.

Researchers have found a genetic link between the risk for COVID-19 infection and the leading cause of vision loss among people age 50 and older, age-related macular degeneration. 

The findings show that COVID and AMD were associated with variations in what is called the PDGFB gene, which has a role in new blood vessel formation and is linked to abnormal blood vessel changes that occur in AMD. The study was published in the Journal of Clinical Medicine. The analysis included genetic data from more than 16,000 people with AMD, more than 50,000 people with COVID, plus control groups.

Age-related macular degeneration is a vision problem that occurs when a part of the retina – the macula – is damaged, according to the American Academy of Ophthalmology. The result is that central vision is lost, but peripheral vision remains normal, so it is difficult to see fine details. For example, a person with AMD can see a clock’s numbers but not its hands. 

“Our analysis lends credence to previously reported clinical studies that found those with AMD have a higher risk for COVID-19 infection and severe disease, and that this increased risk may have a genetic basis,” Boston University researcher Lindsay Farrer, PhD, chief of biomedical genetics, explained in a news release.

Previous research has shown that people with AMD have a 25% increased risk of respiratory failure or death due to COVID, which is higher than other well-known risk factors such as type 2 diabetes (21%) or obesity (13%), according to the news release.

A version of this article first appeared on WebMD.com.

Researchers have found a genetic link between the risk for COVID-19 infection and the leading cause of vision loss among people age 50 and older, age-related macular degeneration. 

The findings show that COVID and AMD were associated with variations in what is called the PDGFB gene, which has a role in new blood vessel formation and is linked to abnormal blood vessel changes that occur in AMD. The study was published in the Journal of Clinical Medicine. The analysis included genetic data from more than 16,000 people with AMD, more than 50,000 people with COVID, plus control groups.

Age-related macular degeneration is a vision problem that occurs when a part of the retina – the macula – is damaged, according to the American Academy of Ophthalmology. The result is that central vision is lost, but peripheral vision remains normal, so it is difficult to see fine details. For example, a person with AMD can see a clock’s numbers but not its hands. 

“Our analysis lends credence to previously reported clinical studies that found those with AMD have a higher risk for COVID-19 infection and severe disease, and that this increased risk may have a genetic basis,” Boston University researcher Lindsay Farrer, PhD, chief of biomedical genetics, explained in a news release.

Previous research has shown that people with AMD have a 25% increased risk of respiratory failure or death due to COVID, which is higher than other well-known risk factors such as type 2 diabetes (21%) or obesity (13%), according to the news release.

A version of this article first appeared on WebMD.com.

Researchers have found a genetic link between the risk for COVID-19 infection and the leading cause of vision loss among people age 50 and older, age-related macular degeneration. 

The findings show that COVID and AMD were associated with variations in what is called the PDGFB gene, which has a role in new blood vessel formation and is linked to abnormal blood vessel changes that occur in AMD. The study was published in the Journal of Clinical Medicine. The analysis included genetic data from more than 16,000 people with AMD, more than 50,000 people with COVID, plus control groups.

Age-related macular degeneration is a vision problem that occurs when a part of the retina – the macula – is damaged, according to the American Academy of Ophthalmology. The result is that central vision is lost, but peripheral vision remains normal, so it is difficult to see fine details. For example, a person with AMD can see a clock’s numbers but not its hands. 

“Our analysis lends credence to previously reported clinical studies that found those with AMD have a higher risk for COVID-19 infection and severe disease, and that this increased risk may have a genetic basis,” Boston University researcher Lindsay Farrer, PhD, chief of biomedical genetics, explained in a news release.

Previous research has shown that people with AMD have a 25% increased risk of respiratory failure or death due to COVID, which is higher than other well-known risk factors such as type 2 diabetes (21%) or obesity (13%), according to the news release.

A version of this article first appeared on WebMD.com.

The administration of IV ketamine over the course of 2 months can improve treatment resistant depression (TRD) and executive function in older adults, findings from a new pilot study suggest.

Results showed nearly 50% of participants responded to ketamine and 25% achieved complete remission from TRD, as measured by scores on the Montgomery-Asberg Depression Rating Scale (MADRS).

“Our pilot study suggests that IV ketamine is well-tolerated, safe, and associated with improvement in late-life TRD,” co-investigator Marie Anne Gebara, MD, assistant professor of psychiatry at the University of Pittsburgh, told this news organization.

Dr. Gebara pointed out the treatment “may not be appropriate for all patients with TRD,” such as those with a history of psychotic symptoms or uncontrolled hypertension; but “it appears to be a promising option.”

The findings were published online in the American Journal of Geriatric Psychiatry.
 

Lack of data in seniors

Although ketamine has been shown in prior research to rapidly reduce suicidal ideation in adults, there has been a lack of data on its efficacy and safety in older adults, the current investigators note.

“Almost 50% of older adults suffering from depression have TRD, which is a leading cause of disability, excess mortality from suicide, and dementia,” Dr. Gebara said.

She added that after two failed trials of antidepressants, “older adults have few evidence-based choices: aripiprazole or bupropion augmentation, transcranial magnetic stimulation, or electroconvulsive therapy. Novel treatments with rapid benefit are needed as long-term outcomes are poor and recurrence rates are high.”

Dr. Gebara and colleagues at five sites (Columbia University, New York State Psychiatric Institute, University of Toronto, University of Pittsburgh, and Washington University in St. Louis) each enrolled five participants aged 60 and older into the pilot study between October 2020 and November 2021, for a total of 25 participants (mean age, 71 years).

Each participant was recruited from patient registries or referred by behavioral health or primary care providers and diagnosed with TRD, which was defined as an episode of major depressive disorder without psychotic features that persisted despite two or more trials of antidepressants including at least one evidence-based second-line treatment.

Participants had to take an oral antidepressant dosage for at least 1 month prior to the start of the IV ketamine infusions, and continue their antidepressant for the length of the trial.

They received IV ketamine twice weekly for 4 weeks. The dosage was weight-dependent.

At the end of the 4 weeks, participants who achieved a MADRS total score of less than 10 or had a 30% or greater reduction from their baseline MADRS score entered another 4-week phase of the trial. This phase consisted of once-weekly administration of IV ketamine.
 

Larger plans

Results showed 15 of the 25 participants (60%) experienced a 30% or higher reduction in MADRS scores in the first phase of the study. The mean change in MADRS total score from the beginning to the end of the first phase was a decrease of 9.4 points (P < .01).

At the end of the continuation phase, half (48%) met criteria for response and 27% met criteria for remission.

After ketamine administration, the researchers also found an improvement in Fluid Cognition Composite Score (Cohen’s d value = .61), indicating a medium to large effect size, and in three measures of executive function.

Overall, adverse events were rare and did not keep patients from participating in the study, the investigators note. Five of the 25 participants reported infusion-induced hypertension that was transient.

Study limitations cited include the small sample size and the absence of randomization and placebo control or comparison treatment.

“We were very pleased with these findings because they establish the safety of this novel intervention in older adults,” Dr. Gebara said.

“After establishing safety and tolerability, we can plan for larger, randomized controlled trials that will allow us to determine the effectiveness of IV ketamine for older adults with TRD,” she added.
 

Multiple mechanisms

In a comment, Gerard Sanacora, MD, PhD, professor of psychiatry at Yale University and director of the Yale Depression Research Program, New Haven, Conn., noted multiple mechanisms likely contribute to the antidepressant effects of ketamine.

Dr. Sanacora has independently researched the effects of ketamine but was not involved with the current study.

“Much of the work to date has focused on the drug’s proximal effects on the glutamatergic neurotransmitter system and the resulting enhancement of adaptive neuroplasticity in several brain regions,” he said.

“However, there is also evidence to suggest other neurotransmitter systems and possibly even neuroinflammatory regulators are also contributing to the effect,” Dr. Sanacora added.

He noted that these mechanisms are also likely amplified by the “hope, optimism, expectations, and improved medical management overall that are known to be associated with treatments that require close monitoring and follow-up with health care providers.”

Dr. Gebara noted that “internal/department funds at each site” were used to support the study. She also reported receiving support from Otsuka US. Disclosures for the other investigators are listed in the original article. Dr. Sanacora has reported having “no major direct conflicts” with the study.

A version of this article first appeared on Medscape.com.

The administration of IV ketamine over the course of 2 months can improve treatment resistant depression (TRD) and executive function in older adults, findings from a new pilot study suggest.

Results showed nearly 50% of participants responded to ketamine and 25% achieved complete remission from TRD, as measured by scores on the Montgomery-Asberg Depression Rating Scale (MADRS).

“Our pilot study suggests that IV ketamine is well-tolerated, safe, and associated with improvement in late-life TRD,” co-investigator Marie Anne Gebara, MD, assistant professor of psychiatry at the University of Pittsburgh, told this news organization.

Dr. Gebara pointed out the treatment “may not be appropriate for all patients with TRD,” such as those with a history of psychotic symptoms or uncontrolled hypertension; but “it appears to be a promising option.”

The findings were published online in the American Journal of Geriatric Psychiatry.
 

Lack of data in seniors

Although ketamine has been shown in prior research to rapidly reduce suicidal ideation in adults, there has been a lack of data on its efficacy and safety in older adults, the current investigators note.

“Almost 50% of older adults suffering from depression have TRD, which is a leading cause of disability, excess mortality from suicide, and dementia,” Dr. Gebara said.

She added that after two failed trials of antidepressants, “older adults have few evidence-based choices: aripiprazole or bupropion augmentation, transcranial magnetic stimulation, or electroconvulsive therapy. Novel treatments with rapid benefit are needed as long-term outcomes are poor and recurrence rates are high.”

Dr. Gebara and colleagues at five sites (Columbia University, New York State Psychiatric Institute, University of Toronto, University of Pittsburgh, and Washington University in St. Louis) each enrolled five participants aged 60 and older into the pilot study between October 2020 and November 2021, for a total of 25 participants (mean age, 71 years).

Each participant was recruited from patient registries or referred by behavioral health or primary care providers and diagnosed with TRD, which was defined as an episode of major depressive disorder without psychotic features that persisted despite two or more trials of antidepressants including at least one evidence-based second-line treatment.

Participants had to take an oral antidepressant dosage for at least 1 month prior to the start of the IV ketamine infusions, and continue their antidepressant for the length of the trial.

They received IV ketamine twice weekly for 4 weeks. The dosage was weight-dependent.

At the end of the 4 weeks, participants who achieved a MADRS total score of less than 10 or had a 30% or greater reduction from their baseline MADRS score entered another 4-week phase of the trial. This phase consisted of once-weekly administration of IV ketamine.
 

Larger plans

Results showed 15 of the 25 participants (60%) experienced a 30% or higher reduction in MADRS scores in the first phase of the study. The mean change in MADRS total score from the beginning to the end of the first phase was a decrease of 9.4 points (P < .01).

At the end of the continuation phase, half (48%) met criteria for response and 27% met criteria for remission.

After ketamine administration, the researchers also found an improvement in Fluid Cognition Composite Score (Cohen’s d value = .61), indicating a medium to large effect size, and in three measures of executive function.

Overall, adverse events were rare and did not keep patients from participating in the study, the investigators note. Five of the 25 participants reported infusion-induced hypertension that was transient.

Study limitations cited include the small sample size and the absence of randomization and placebo control or comparison treatment.

“We were very pleased with these findings because they establish the safety of this novel intervention in older adults,” Dr. Gebara said.

“After establishing safety and tolerability, we can plan for larger, randomized controlled trials that will allow us to determine the effectiveness of IV ketamine for older adults with TRD,” she added.
 

Multiple mechanisms

In a comment, Gerard Sanacora, MD, PhD, professor of psychiatry at Yale University and director of the Yale Depression Research Program, New Haven, Conn., noted multiple mechanisms likely contribute to the antidepressant effects of ketamine.

Dr. Sanacora has independently researched the effects of ketamine but was not involved with the current study.

“Much of the work to date has focused on the drug’s proximal effects on the glutamatergic neurotransmitter system and the resulting enhancement of adaptive neuroplasticity in several brain regions,” he said.

“However, there is also evidence to suggest other neurotransmitter systems and possibly even neuroinflammatory regulators are also contributing to the effect,” Dr. Sanacora added.

He noted that these mechanisms are also likely amplified by the “hope, optimism, expectations, and improved medical management overall that are known to be associated with treatments that require close monitoring and follow-up with health care providers.”

Dr. Gebara noted that “internal/department funds at each site” were used to support the study. She also reported receiving support from Otsuka US. Disclosures for the other investigators are listed in the original article. Dr. Sanacora has reported having “no major direct conflicts” with the study.

A version of this article first appeared on Medscape.com.

The administration of IV ketamine over the course of 2 months can improve treatment resistant depression (TRD) and executive function in older adults, findings from a new pilot study suggest.

Results showed nearly 50% of participants responded to ketamine and 25% achieved complete remission from TRD, as measured by scores on the Montgomery-Asberg Depression Rating Scale (MADRS).

“Our pilot study suggests that IV ketamine is well-tolerated, safe, and associated with improvement in late-life TRD,” co-investigator Marie Anne Gebara, MD, assistant professor of psychiatry at the University of Pittsburgh, told this news organization.

Dr. Gebara pointed out the treatment “may not be appropriate for all patients with TRD,” such as those with a history of psychotic symptoms or uncontrolled hypertension; but “it appears to be a promising option.”

The findings were published online in the American Journal of Geriatric Psychiatry.
 

Lack of data in seniors

Although ketamine has been shown in prior research to rapidly reduce suicidal ideation in adults, there has been a lack of data on its efficacy and safety in older adults, the current investigators note.

“Almost 50% of older adults suffering from depression have TRD, which is a leading cause of disability, excess mortality from suicide, and dementia,” Dr. Gebara said.

She added that after two failed trials of antidepressants, “older adults have few evidence-based choices: aripiprazole or bupropion augmentation, transcranial magnetic stimulation, or electroconvulsive therapy. Novel treatments with rapid benefit are needed as long-term outcomes are poor and recurrence rates are high.”

Dr. Gebara and colleagues at five sites (Columbia University, New York State Psychiatric Institute, University of Toronto, University of Pittsburgh, and Washington University in St. Louis) each enrolled five participants aged 60 and older into the pilot study between October 2020 and November 2021, for a total of 25 participants (mean age, 71 years).

Each participant was recruited from patient registries or referred by behavioral health or primary care providers and diagnosed with TRD, which was defined as an episode of major depressive disorder without psychotic features that persisted despite two or more trials of antidepressants including at least one evidence-based second-line treatment.

Participants had to take an oral antidepressant dosage for at least 1 month prior to the start of the IV ketamine infusions, and continue their antidepressant for the length of the trial.

They received IV ketamine twice weekly for 4 weeks. The dosage was weight-dependent.

At the end of the 4 weeks, participants who achieved a MADRS total score of less than 10 or had a 30% or greater reduction from their baseline MADRS score entered another 4-week phase of the trial. This phase consisted of once-weekly administration of IV ketamine.
 

Larger plans

Results showed 15 of the 25 participants (60%) experienced a 30% or higher reduction in MADRS scores in the first phase of the study. The mean change in MADRS total score from the beginning to the end of the first phase was a decrease of 9.4 points (P < .01).

At the end of the continuation phase, half (48%) met criteria for response and 27% met criteria for remission.

After ketamine administration, the researchers also found an improvement in Fluid Cognition Composite Score (Cohen’s d value = .61), indicating a medium to large effect size, and in three measures of executive function.

Overall, adverse events were rare and did not keep patients from participating in the study, the investigators note. Five of the 25 participants reported infusion-induced hypertension that was transient.

Study limitations cited include the small sample size and the absence of randomization and placebo control or comparison treatment.

“We were very pleased with these findings because they establish the safety of this novel intervention in older adults,” Dr. Gebara said.

“After establishing safety and tolerability, we can plan for larger, randomized controlled trials that will allow us to determine the effectiveness of IV ketamine for older adults with TRD,” she added.
 

Multiple mechanisms

In a comment, Gerard Sanacora, MD, PhD, professor of psychiatry at Yale University and director of the Yale Depression Research Program, New Haven, Conn., noted multiple mechanisms likely contribute to the antidepressant effects of ketamine.

Dr. Sanacora has independently researched the effects of ketamine but was not involved with the current study.

“Much of the work to date has focused on the drug’s proximal effects on the glutamatergic neurotransmitter system and the resulting enhancement of adaptive neuroplasticity in several brain regions,” he said.

“However, there is also evidence to suggest other neurotransmitter systems and possibly even neuroinflammatory regulators are also contributing to the effect,” Dr. Sanacora added.

He noted that these mechanisms are also likely amplified by the “hope, optimism, expectations, and improved medical management overall that are known to be associated with treatments that require close monitoring and follow-up with health care providers.”

Dr. Gebara noted that “internal/department funds at each site” were used to support the study. She also reported receiving support from Otsuka US. Disclosures for the other investigators are listed in the original article. Dr. Sanacora has reported having “no major direct conflicts” with the study.

A version of this article first appeared on Medscape.com.

The obvious first statement is that it’s neither wise nor appropriate to speculate on the specifics of Damar Hamlin’s cardiac event during a football game on Jan. 2 (including the possibility of commotio cordis) or his ongoing care. The public nature of his collapse induces intense curiosity but people with illness deserve privacy. Privacy in health care is in short supply. I disagree strongly with those who say his doctors ought to be giving public updates. That’s up to the family.

But there are important general concepts to consider about this incident. These include ...

Cardiac arrest can happen to anyone

People with structural heart disease or other chronic illnesses have a higher risk of arrhythmia, but the notion that athletes are immune from cardiac arrest is wrong. This sentence almost seems too obvious to write, but to this day, I hear clinicians express surprise that an athletic person has heart disease.

Survival turns on rapid and effective intervention

In the old days of electrophysiology, we used to test implantable cardioverter-defibrillators during an implant procedure by inducing ventricular fibrillation (VF) and watching the device convert it. Thankfully, trials have shown that this is no longer necessary for most implants.

When you induce VF In the EP lab, you learn quickly that a) it causes loss of consciousness in a matter of seconds, b) rapid defibrillation restores consciousness, often without the patients knowing or remembering they passed out, and c) the failure of the shock to terminate VF results in deterioration in a matter of 1-2 minutes. Even 1 minute in VF feels so long.

Need is an appropriate word in VF treatment

Clinicians often use the verb need. As in, this patient needs this pill or this procedure. It’s rarely appropriate.

But in the case of treating VF, patients truly need rapid defibrillation. Survival of out-of-hospital cardiac arrest is low because there just aren’t enough automated external defibrillators (AEDs) or people trained to use them. A study of patients who had out-of-hospital cardiac arrest in Denmark found that 30-day survival almost doubled (28.8% vs. 16.4%), when the nearest AED was accessible.

Bystanders must act

The public messages are simple: If a person loses consciousness in front of you, and is not breathing normally, assume it is a cardiac arrest, call 911 to get professional help, and start hands-only chest compressions. Don’t spend time checking for a pulse or trying to wake the person. If this is not a cardiac arrest, they will soon tell you to stop compressing their chest. Seconds matter.

Chest compressions are important but what is really needed is defibrillation. A crucial step in CPR is to send someone to get an AED and get the pads attached. If this is a shockable rhythm, deliver the shock. Hamlin’s collapse emphasizes the importance of the AED; without it, his survival to the hospital would have been unlikely.

Widespread preparticipation screening of young athletes remains a bad idea

Whenever cardiac arrest occurs in an athlete, in such a public way, people think about prevention. Surely it is better to prevent such an event than react to it, goes the thinking. The argument against this idea has four prongs:

The incidence of cardiac disease in a young athlete is extremely low, which sets up a situation where most “positive” tests are false positive. A false positive screening ECG or echocardiogram can create harm in multiple ways. One is the risk from downstream procedures, but worse is the inappropriate disqualification from sport. Healthwise, few harms could be greater than creating long-term fear of exercise in someone.

There is also the problem of false-negative screening tests. An ECG may be normal in the setting of hypertrophic cardiomyopathy. And a normal echocardiogram does not exclude arrhythmogenic right ventricular cardiomyopathy or other genetic causes of cardiac arrest. In a 2018 study from a major sports cardiology center in London, 6 of the 8 sudden cardiac deaths in their series were in athletes who had no detectable abnormalities on screening.

Even when disease is found, it’s not clear that prohibiting participation in sports prevents sudden death. Many previous class III recommendations against participation in sport now carry class II – may be considered – designations.

Finally, screening for any disease loses value as treatments improve. Public education regarding rapid intervention with CPR and AED use is the best treatment option. A great example is the case of Christian Erikson, a Danish soccer player who suffered cardiac arrest during a match at the European Championships in 2021 and was rapidly defibrillated on the field. Therapy was so effective that he was conscious and able to wave to fans on his way out of the stadium. He has now returned to elite competition.

Proponents of screening might oppose my take by saying that National Football League players are intensely screened. But this is different from widespread screening of high school and college athletes. It might sound harsh to say, but professional teams have dualities of interests in the health of their athletes given the million-dollar contracts.

What’s more, professional teams can afford to hire expert cardiologists to perform the testing. This would likely reduce the rate of false-positive findings, compared with screening in the community setting. I often have young people referred to me because of asymptomatic bradycardia found during athletic screening – an obviously normal finding.

Conclusions

As long as there are sports, there will be athletes who suffer cardiac arrest.

We can both hope for Hamlin’s full recovery and learn lessons to help reduce the rate of death from out-of-hospital cardiac arrest. This mostly involves education on how to help fellow humans and a public health commitment to access to AEDs.

John Mandrola, MD, practices cardiac electrophysiology in Louisville, Ky. and is a writer and podcaster for Medscape. He has disclosed no relevant financial relationships. A version of this article first appeared on Medscape.com.

The obvious first statement is that it’s neither wise nor appropriate to speculate on the specifics of Damar Hamlin’s cardiac event during a football game on Jan. 2 (including the possibility of commotio cordis) or his ongoing care. The public nature of his collapse induces intense curiosity but people with illness deserve privacy. Privacy in health care is in short supply. I disagree strongly with those who say his doctors ought to be giving public updates. That’s up to the family.

But there are important general concepts to consider about this incident. These include ...

Cardiac arrest can happen to anyone

People with structural heart disease or other chronic illnesses have a higher risk of arrhythmia, but the notion that athletes are immune from cardiac arrest is wrong. This sentence almost seems too obvious to write, but to this day, I hear clinicians express surprise that an athletic person has heart disease.

Survival turns on rapid and effective intervention

In the old days of electrophysiology, we used to test implantable cardioverter-defibrillators during an implant procedure by inducing ventricular fibrillation (VF) and watching the device convert it. Thankfully, trials have shown that this is no longer necessary for most implants.

When you induce VF In the EP lab, you learn quickly that a) it causes loss of consciousness in a matter of seconds, b) rapid defibrillation restores consciousness, often without the patients knowing or remembering they passed out, and c) the failure of the shock to terminate VF results in deterioration in a matter of 1-2 minutes. Even 1 minute in VF feels so long.

Need is an appropriate word in VF treatment

Clinicians often use the verb need. As in, this patient needs this pill or this procedure. It’s rarely appropriate.

But in the case of treating VF, patients truly need rapid defibrillation. Survival of out-of-hospital cardiac arrest is low because there just aren’t enough automated external defibrillators (AEDs) or people trained to use them. A study of patients who had out-of-hospital cardiac arrest in Denmark found that 30-day survival almost doubled (28.8% vs. 16.4%), when the nearest AED was accessible.

Bystanders must act

The public messages are simple: If a person loses consciousness in front of you, and is not breathing normally, assume it is a cardiac arrest, call 911 to get professional help, and start hands-only chest compressions. Don’t spend time checking for a pulse or trying to wake the person. If this is not a cardiac arrest, they will soon tell you to stop compressing their chest. Seconds matter.

Chest compressions are important but what is really needed is defibrillation. A crucial step in CPR is to send someone to get an AED and get the pads attached. If this is a shockable rhythm, deliver the shock. Hamlin’s collapse emphasizes the importance of the AED; without it, his survival to the hospital would have been unlikely.

Widespread preparticipation screening of young athletes remains a bad idea

Whenever cardiac arrest occurs in an athlete, in such a public way, people think about prevention. Surely it is better to prevent such an event than react to it, goes the thinking. The argument against this idea has four prongs:

The incidence of cardiac disease in a young athlete is extremely low, which sets up a situation where most “positive” tests are false positive. A false positive screening ECG or echocardiogram can create harm in multiple ways. One is the risk from downstream procedures, but worse is the inappropriate disqualification from sport. Healthwise, few harms could be greater than creating long-term fear of exercise in someone.

There is also the problem of false-negative screening tests. An ECG may be normal in the setting of hypertrophic cardiomyopathy. And a normal echocardiogram does not exclude arrhythmogenic right ventricular cardiomyopathy or other genetic causes of cardiac arrest. In a 2018 study from a major sports cardiology center in London, 6 of the 8 sudden cardiac deaths in their series were in athletes who had no detectable abnormalities on screening.

Even when disease is found, it’s not clear that prohibiting participation in sports prevents sudden death. Many previous class III recommendations against participation in sport now carry class II – may be considered – designations.

Finally, screening for any disease loses value as treatments improve. Public education regarding rapid intervention with CPR and AED use is the best treatment option. A great example is the case of Christian Erikson, a Danish soccer player who suffered cardiac arrest during a match at the European Championships in 2021 and was rapidly defibrillated on the field. Therapy was so effective that he was conscious and able to wave to fans on his way out of the stadium. He has now returned to elite competition.

Proponents of screening might oppose my take by saying that National Football League players are intensely screened. But this is different from widespread screening of high school and college athletes. It might sound harsh to say, but professional teams have dualities of interests in the health of their athletes given the million-dollar contracts.

What’s more, professional teams can afford to hire expert cardiologists to perform the testing. This would likely reduce the rate of false-positive findings, compared with screening in the community setting. I often have young people referred to me because of asymptomatic bradycardia found during athletic screening – an obviously normal finding.

Conclusions

As long as there are sports, there will be athletes who suffer cardiac arrest.

We can both hope for Hamlin’s full recovery and learn lessons to help reduce the rate of death from out-of-hospital cardiac arrest. This mostly involves education on how to help fellow humans and a public health commitment to access to AEDs.

John Mandrola, MD, practices cardiac electrophysiology in Louisville, Ky. and is a writer and podcaster for Medscape. He has disclosed no relevant financial relationships. A version of this article first appeared on Medscape.com.

The obvious first statement is that it’s neither wise nor appropriate to speculate on the specifics of Damar Hamlin’s cardiac event during a football game on Jan. 2 (including the possibility of commotio cordis) or his ongoing care. The public nature of his collapse induces intense curiosity but people with illness deserve privacy. Privacy in health care is in short supply. I disagree strongly with those who say his doctors ought to be giving public updates. That’s up to the family.

But there are important general concepts to consider about this incident. These include ...

Cardiac arrest can happen to anyone

People with structural heart disease or other chronic illnesses have a higher risk of arrhythmia, but the notion that athletes are immune from cardiac arrest is wrong. This sentence almost seems too obvious to write, but to this day, I hear clinicians express surprise that an athletic person has heart disease.

Survival turns on rapid and effective intervention

In the old days of electrophysiology, we used to test implantable cardioverter-defibrillators during an implant procedure by inducing ventricular fibrillation (VF) and watching the device convert it. Thankfully, trials have shown that this is no longer necessary for most implants.

When you induce VF In the EP lab, you learn quickly that a) it causes loss of consciousness in a matter of seconds, b) rapid defibrillation restores consciousness, often without the patients knowing or remembering they passed out, and c) the failure of the shock to terminate VF results in deterioration in a matter of 1-2 minutes. Even 1 minute in VF feels so long.

Need is an appropriate word in VF treatment

Clinicians often use the verb need. As in, this patient needs this pill or this procedure. It’s rarely appropriate.

But in the case of treating VF, patients truly need rapid defibrillation. Survival of out-of-hospital cardiac arrest is low because there just aren’t enough automated external defibrillators (AEDs) or people trained to use them. A study of patients who had out-of-hospital cardiac arrest in Denmark found that 30-day survival almost doubled (28.8% vs. 16.4%), when the nearest AED was accessible.

Bystanders must act

The public messages are simple: If a person loses consciousness in front of you, and is not breathing normally, assume it is a cardiac arrest, call 911 to get professional help, and start hands-only chest compressions. Don’t spend time checking for a pulse or trying to wake the person. If this is not a cardiac arrest, they will soon tell you to stop compressing their chest. Seconds matter.

Chest compressions are important but what is really needed is defibrillation. A crucial step in CPR is to send someone to get an AED and get the pads attached. If this is a shockable rhythm, deliver the shock. Hamlin’s collapse emphasizes the importance of the AED; without it, his survival to the hospital would have been unlikely.

Widespread preparticipation screening of young athletes remains a bad idea

Whenever cardiac arrest occurs in an athlete, in such a public way, people think about prevention. Surely it is better to prevent such an event than react to it, goes the thinking. The argument against this idea has four prongs:

The incidence of cardiac disease in a young athlete is extremely low, which sets up a situation where most “positive” tests are false positive. A false positive screening ECG or echocardiogram can create harm in multiple ways. One is the risk from downstream procedures, but worse is the inappropriate disqualification from sport. Healthwise, few harms could be greater than creating long-term fear of exercise in someone.

There is also the problem of false-negative screening tests. An ECG may be normal in the setting of hypertrophic cardiomyopathy. And a normal echocardiogram does not exclude arrhythmogenic right ventricular cardiomyopathy or other genetic causes of cardiac arrest. In a 2018 study from a major sports cardiology center in London, 6 of the 8 sudden cardiac deaths in their series were in athletes who had no detectable abnormalities on screening.

Even when disease is found, it’s not clear that prohibiting participation in sports prevents sudden death. Many previous class III recommendations against participation in sport now carry class II – may be considered – designations.

Finally, screening for any disease loses value as treatments improve. Public education regarding rapid intervention with CPR and AED use is the best treatment option. A great example is the case of Christian Erikson, a Danish soccer player who suffered cardiac arrest during a match at the European Championships in 2021 and was rapidly defibrillated on the field. Therapy was so effective that he was conscious and able to wave to fans on his way out of the stadium. He has now returned to elite competition.

Proponents of screening might oppose my take by saying that National Football League players are intensely screened. But this is different from widespread screening of high school and college athletes. It might sound harsh to say, but professional teams have dualities of interests in the health of their athletes given the million-dollar contracts.

What’s more, professional teams can afford to hire expert cardiologists to perform the testing. This would likely reduce the rate of false-positive findings, compared with screening in the community setting. I often have young people referred to me because of asymptomatic bradycardia found during athletic screening – an obviously normal finding.

Conclusions

As long as there are sports, there will be athletes who suffer cardiac arrest.

We can both hope for Hamlin’s full recovery and learn lessons to help reduce the rate of death from out-of-hospital cardiac arrest. This mostly involves education on how to help fellow humans and a public health commitment to access to AEDs.

John Mandrola, MD, practices cardiac electrophysiology in Louisville, Ky. and is a writer and podcaster for Medscape. He has disclosed no relevant financial relationships. A version of this article first appeared on Medscape.com.

Clinical guidelines recommend use of exacerbation history in choosing therapies to predict the risk for chronic obstructive pulmonary disease exacerbations, but an analysis of data from three different clinical studies has found that exacerbation history alone is not the most accurate risk-prediction tool – and that it may even cause harm in some situations.

“Our results present a cautionary tale for the potential risk of harm to patients when naively applying risk stratification algorithms across different clinical settings,” lead author Joseph Khoa Ho, PharmD, a master’s candidate in pharmaceutical sciences at the University of British Columbia, Vancouver, told this news organization.

“We show that risk-prediction models have better accuracy than exacerbation history alone for predicting the future risk of COPD exacerbations,” he said. “However, the prediction models required re-evaluation and setting-specific recalibration in order to yield higher clinical utility.”

The study, known as IMPACT, analyzed three trials that enrolled 4,107 patients at varying levels of moderate or severe exacerbation risks: the placebo arm of the Study to Understand Mortality and Morbidity in COPD (SUMMIT; N = 2,421); the Long-term Oxygen Treatment Trial (LOTT; N = 595); and the placebo arm of the Towards a Revolution in COPD Health trial (TORCH; N = 1,091). The exacerbation risks were low, medium, and high in the three respective trials.

The study, published online in the journal CHEST, compared the performance of three risk-stratification algorithms: exacerbation history; the model that Loes C.M. Bertens, PhD, and colleagues in the Netherlands developed in 2013; and the latest version of the Acute COPD Exacerbation Prediction Tool, known as ACCEPT.
 

Results of the analysis

The study used area under the curve (AUC), a method of evaluating effectiveness or efficiency, to compare performance of the prediction algorithms. ACCEPT outperformed exacerbation history and the Bertens algorithm in all the LOTT (medium risk) and TORCH (high risk) samples, both of which were statistically significant. In SUMMIT (low risk), Bertens and ACCEPT outperformed exacerbation history, which was statistically significant.

The AUC for exacerbation history alone in predicting future exacerbations in SUMMIT, LOTT, and TORCH was 0.59 (95% confidence interval, 0.57-0.61), 0.63 (95% CI, 0.59-0.67), and 0.65 (95% CI, 0.63-0.68), respectively. Bertens had a higher AUC, compared with exacerbation history alone in SUMMIT (increase of 0.10, P < .001) and TORCH (increase of 0.05, P < .001), but not in LOTT (increase of 0.01, P = .84).

ACCEPT had higher AUC, compared with exacerbation history alone in all study samples, by 0.08 (P < .001), 0.07 (P = .001) and 0.10 (P < .001), respectively. Compared with Bertens, ACCEPT had higher AUC by 0.06 (P = .001) in LOTT and 0.05 (P < .001) in TORCH, whereas the AUCs were not different in SUMMIT (change of –0.02, P = .16).
 

Study rationale

Senior author Mohsen Sadatsafavi, MD, PhD, associate professor of pharmaceutical sciences at the University of British Columbia, told this news organization that this study was inspired by a study in cardiology earlier in 2022 that found that the performance of the multitude of risk-prediction tools used to evaluate cardiovascular disease risk can vary widely if they’re not calibrated for new patient populations.

“The main finding was that exacerbation history alone can be harmful even if it is applied at different risk levels,” Dr. Sadatsafavi said of the IMPACT study. “No algorithm could be universally applicable, but exacerbation history has a very high chance of being worse than not doing any risk stratification at all and simply giving medication to all patients.”

Exacerbation history was considered harmful because it generated a lower net benefit than the either Bertens or ACCEPT, the IMPACT study found.

The benefit of the two risk-prediction tools is that they can be recalibrated, Dr. Sadatsafavi said. “You don’t have that luxury with exacerbation history, because it’s just a fixed positive or negative history,” he said. “We need to be quite cognizant of the difference in lung attacks in different populations and the fact that exacerbation history has very different performance in different groups and might be harmful when applied in certain populations. We suggest the use of the risk-stratification tools as a better proper statistical model.”
 

Expert comment

“As the authors point out, current guidelines for COPD management recommend preventive exacerbation therapy considering the patient’s exacerbation history,” Mary Jo S. Farmer, MD, PhD, assistant professor at the University of Massachusetts Chan Medical School-Baystate, Worcester, said via email. “However, this strategy has demonstrated harm in some situations.”

She noted that the multivariable prediction models were more accurate than exacerbation history alone for predicting 12-month risk of moderate/severe COPD exacerbations but that no algorithm was superior in clinical utility across all samples. 

“The authors conclude that the highest accuracy of a risk prediction model can be achieved when the model is recalibrated based on the baseline exacerbation risk of the study population in question,” Dr. Farmer added. 

The study received funding from the Canadian Institutes of Health Research. Dr. Ho, Dr. Sadatsafavi, and Dr. Farmer report no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Clinical guidelines recommend use of exacerbation history in choosing therapies to predict the risk for chronic obstructive pulmonary disease exacerbations, but an analysis of data from three different clinical studies has found that exacerbation history alone is not the most accurate risk-prediction tool – and that it may even cause harm in some situations.

“Our results present a cautionary tale for the potential risk of harm to patients when naively applying risk stratification algorithms across different clinical settings,” lead author Joseph Khoa Ho, PharmD, a master’s candidate in pharmaceutical sciences at the University of British Columbia, Vancouver, told this news organization.

“We show that risk-prediction models have better accuracy than exacerbation history alone for predicting the future risk of COPD exacerbations,” he said. “However, the prediction models required re-evaluation and setting-specific recalibration in order to yield higher clinical utility.”

The study, known as IMPACT, analyzed three trials that enrolled 4,107 patients at varying levels of moderate or severe exacerbation risks: the placebo arm of the Study to Understand Mortality and Morbidity in COPD (SUMMIT; N = 2,421); the Long-term Oxygen Treatment Trial (LOTT; N = 595); and the placebo arm of the Towards a Revolution in COPD Health trial (TORCH; N = 1,091). The exacerbation risks were low, medium, and high in the three respective trials.

The study, published online in the journal CHEST, compared the performance of three risk-stratification algorithms: exacerbation history; the model that Loes C.M. Bertens, PhD, and colleagues in the Netherlands developed in 2013; and the latest version of the Acute COPD Exacerbation Prediction Tool, known as ACCEPT.
 

Results of the analysis

The study used area under the curve (AUC), a method of evaluating effectiveness or efficiency, to compare performance of the prediction algorithms. ACCEPT outperformed exacerbation history and the Bertens algorithm in all the LOTT (medium risk) and TORCH (high risk) samples, both of which were statistically significant. In SUMMIT (low risk), Bertens and ACCEPT outperformed exacerbation history, which was statistically significant.

The AUC for exacerbation history alone in predicting future exacerbations in SUMMIT, LOTT, and TORCH was 0.59 (95% confidence interval, 0.57-0.61), 0.63 (95% CI, 0.59-0.67), and 0.65 (95% CI, 0.63-0.68), respectively. Bertens had a higher AUC, compared with exacerbation history alone in SUMMIT (increase of 0.10, P < .001) and TORCH (increase of 0.05, P < .001), but not in LOTT (increase of 0.01, P = .84).

ACCEPT had higher AUC, compared with exacerbation history alone in all study samples, by 0.08 (P < .001), 0.07 (P = .001) and 0.10 (P < .001), respectively. Compared with Bertens, ACCEPT had higher AUC by 0.06 (P = .001) in LOTT and 0.05 (P < .001) in TORCH, whereas the AUCs were not different in SUMMIT (change of –0.02, P = .16).
 

Study rationale

Senior author Mohsen Sadatsafavi, MD, PhD, associate professor of pharmaceutical sciences at the University of British Columbia, told this news organization that this study was inspired by a study in cardiology earlier in 2022 that found that the performance of the multitude of risk-prediction tools used to evaluate cardiovascular disease risk can vary widely if they’re not calibrated for new patient populations.

“The main finding was that exacerbation history alone can be harmful even if it is applied at different risk levels,” Dr. Sadatsafavi said of the IMPACT study. “No algorithm could be universally applicable, but exacerbation history has a very high chance of being worse than not doing any risk stratification at all and simply giving medication to all patients.”

Exacerbation history was considered harmful because it generated a lower net benefit than the either Bertens or ACCEPT, the IMPACT study found.

The benefit of the two risk-prediction tools is that they can be recalibrated, Dr. Sadatsafavi said. “You don’t have that luxury with exacerbation history, because it’s just a fixed positive or negative history,” he said. “We need to be quite cognizant of the difference in lung attacks in different populations and the fact that exacerbation history has very different performance in different groups and might be harmful when applied in certain populations. We suggest the use of the risk-stratification tools as a better proper statistical model.”
 

Expert comment

“As the authors point out, current guidelines for COPD management recommend preventive exacerbation therapy considering the patient’s exacerbation history,” Mary Jo S. Farmer, MD, PhD, assistant professor at the University of Massachusetts Chan Medical School-Baystate, Worcester, said via email. “However, this strategy has demonstrated harm in some situations.”

She noted that the multivariable prediction models were more accurate than exacerbation history alone for predicting 12-month risk of moderate/severe COPD exacerbations but that no algorithm was superior in clinical utility across all samples. 

“The authors conclude that the highest accuracy of a risk prediction model can be achieved when the model is recalibrated based on the baseline exacerbation risk of the study population in question,” Dr. Farmer added. 

The study received funding from the Canadian Institutes of Health Research. Dr. Ho, Dr. Sadatsafavi, and Dr. Farmer report no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Clinical guidelines recommend use of exacerbation history in choosing therapies to predict the risk for chronic obstructive pulmonary disease exacerbations, but an analysis of data from three different clinical studies has found that exacerbation history alone is not the most accurate risk-prediction tool – and that it may even cause harm in some situations.

“Our results present a cautionary tale for the potential risk of harm to patients when naively applying risk stratification algorithms across different clinical settings,” lead author Joseph Khoa Ho, PharmD, a master’s candidate in pharmaceutical sciences at the University of British Columbia, Vancouver, told this news organization.

“We show that risk-prediction models have better accuracy than exacerbation history alone for predicting the future risk of COPD exacerbations,” he said. “However, the prediction models required re-evaluation and setting-specific recalibration in order to yield higher clinical utility.”

The study, known as IMPACT, analyzed three trials that enrolled 4,107 patients at varying levels of moderate or severe exacerbation risks: the placebo arm of the Study to Understand Mortality and Morbidity in COPD (SUMMIT; N = 2,421); the Long-term Oxygen Treatment Trial (LOTT; N = 595); and the placebo arm of the Towards a Revolution in COPD Health trial (TORCH; N = 1,091). The exacerbation risks were low, medium, and high in the three respective trials.

The study, published online in the journal CHEST, compared the performance of three risk-stratification algorithms: exacerbation history; the model that Loes C.M. Bertens, PhD, and colleagues in the Netherlands developed in 2013; and the latest version of the Acute COPD Exacerbation Prediction Tool, known as ACCEPT.
 

Results of the analysis

The study used area under the curve (AUC), a method of evaluating effectiveness or efficiency, to compare performance of the prediction algorithms. ACCEPT outperformed exacerbation history and the Bertens algorithm in all the LOTT (medium risk) and TORCH (high risk) samples, both of which were statistically significant. In SUMMIT (low risk), Bertens and ACCEPT outperformed exacerbation history, which was statistically significant.

The AUC for exacerbation history alone in predicting future exacerbations in SUMMIT, LOTT, and TORCH was 0.59 (95% confidence interval, 0.57-0.61), 0.63 (95% CI, 0.59-0.67), and 0.65 (95% CI, 0.63-0.68), respectively. Bertens had a higher AUC, compared with exacerbation history alone in SUMMIT (increase of 0.10, P < .001) and TORCH (increase of 0.05, P < .001), but not in LOTT (increase of 0.01, P = .84).

ACCEPT had higher AUC, compared with exacerbation history alone in all study samples, by 0.08 (P < .001), 0.07 (P = .001) and 0.10 (P < .001), respectively. Compared with Bertens, ACCEPT had higher AUC by 0.06 (P = .001) in LOTT and 0.05 (P < .001) in TORCH, whereas the AUCs were not different in SUMMIT (change of –0.02, P = .16).
 

Study rationale

Senior author Mohsen Sadatsafavi, MD, PhD, associate professor of pharmaceutical sciences at the University of British Columbia, told this news organization that this study was inspired by a study in cardiology earlier in 2022 that found that the performance of the multitude of risk-prediction tools used to evaluate cardiovascular disease risk can vary widely if they’re not calibrated for new patient populations.

“The main finding was that exacerbation history alone can be harmful even if it is applied at different risk levels,” Dr. Sadatsafavi said of the IMPACT study. “No algorithm could be universally applicable, but exacerbation history has a very high chance of being worse than not doing any risk stratification at all and simply giving medication to all patients.”

Exacerbation history was considered harmful because it generated a lower net benefit than the either Bertens or ACCEPT, the IMPACT study found.

The benefit of the two risk-prediction tools is that they can be recalibrated, Dr. Sadatsafavi said. “You don’t have that luxury with exacerbation history, because it’s just a fixed positive or negative history,” he said. “We need to be quite cognizant of the difference in lung attacks in different populations and the fact that exacerbation history has very different performance in different groups and might be harmful when applied in certain populations. We suggest the use of the risk-stratification tools as a better proper statistical model.”
 

Expert comment

“As the authors point out, current guidelines for COPD management recommend preventive exacerbation therapy considering the patient’s exacerbation history,” Mary Jo S. Farmer, MD, PhD, assistant professor at the University of Massachusetts Chan Medical School-Baystate, Worcester, said via email. “However, this strategy has demonstrated harm in some situations.”

She noted that the multivariable prediction models were more accurate than exacerbation history alone for predicting 12-month risk of moderate/severe COPD exacerbations but that no algorithm was superior in clinical utility across all samples. 

“The authors conclude that the highest accuracy of a risk prediction model can be achieved when the model is recalibrated based on the baseline exacerbation risk of the study population in question,” Dr. Farmer added. 

The study received funding from the Canadian Institutes of Health Research. Dr. Ho, Dr. Sadatsafavi, and Dr. Farmer report no relevant financial relationships.

A version of this article first appeared on Medscape.com.

More than a quarter of cardiologists in an international survey reported experiencing mental health conditions ranging from anxiety or anger issues to major depression or other psychiatric disorders.  

Such conditions varied in prevalence by cardiology subspecialty and years in the field, were more common in women than in men, and were closely linked to enduring hostile work environments and other strains of professional life.

The survey, conducted only months before the COVID-19 pandemic and with its share of limitations, still paints a picture that’s not pretty.

For example, mental health concerns were reported by about 42% of respondents who cited a hostile work environment, defined as workplace experience of discrimination based on age, sex, religion, race or ethnicity, or emotional or sexual harassment. Conversely, the prevalence of these concerns reached only 17% among those without such workplace conditions.

The study shows substantial overlap between cardiologists reporting hostility at work and those with mental health concerns, “and that was a significant finding,” Garima Sharma, MD, Johns Hopkins University, Baltimore, said in an interview.

Still, only 31% of male and 42% of female cardiologists (P < .001) reporting mental health concerns also said they had sought professional help either within or outside their own institutions.

That means “there is a lot of silent suffering” in the field, said Dr. Sharma, who is lead author on the study, published in the Journal of the American College of Cardiology.
 

Bringing back the conversation

The survey findings, she added, point to at least two potential ways the cardiology community can strive to diminish what may be a major underlying cause of the mental health concerns and their consequences.

“If you work towards reducing hostility at work and making mental health a priority for your workforce, then those experiencing these types of egregious conditions based on age, gender, race, ethnicity, or sexual orientation are less likely to be harmed.”

Mental health concerns among cardiologists are seldom openly discussed, so the current study can be “a way to bring them back into the conversation,” Dr. Sharma said. Clinician mental health “is extremely important because it directly impacts patient care and productivity.”

The survey’s reported mental health conditions “are an issue across the board in medicine, and amongst our medical students as well,” senior author Laxmi S. Mehta, MD, professor of internal medicine at Ohio State University, Columbus, said in an interview. The current study provides new details about their prevalence and predictors in cardiology and, she hopes, may improve the field’s awareness of and efforts to address the problem.

“We need to support those who have underlying mental health conditions, as well as improve the work environment to reduce contributory factors to mental illnesses. And we also need to work on reducing the stigma associated with seeking treatment and on reducing the barriers to receiving treatment,” said Dr. Mehta, who chairs the Workgroup on Clinician Well-Being of the ACC, which conducted the survey in 2019.
 

A global perspective

Cardiologists in Africa, the Americas, Asia, Europe, the Middle East, and Oceania – 5,890 in all – responded to mental health questions on the survey, which was novel for its global reach and insights across continents and cultures.

Respondents in South America and Central America reported the highest prevalences of mental health concerns, outliers at about 39% and 33%, respectively. Rates for most other geographic regions ranged narrowly from about 20% to 26%, the lowest reported in Asia and the Middle East.

Dr. Sharma acknowledged that the countries probably varied widely in social and cultural factors likely to influence survey responses, such as interpretation of the questionnaire’s mental health terminology or the degree to which the disorders are stigmatized.

“I think it’s hard to say how people may or may not respond culturally to a certain word or metric,” she said. But on the survey results, “whether you’re practicing in rural America, in rural India, or in the United Arab Emirates, Oceania, or Eastern Europe, there is a level of consistency, across the board, in what people are recognizing as mental health conditions.”
 

Junior vs. senior physicians

The global perspective “is a nice positive of the study, and the high rates in Central America and South America I think were something the field was not aware of and are an important contribution,” Srijan Sen, MD, PhD, said in an interview.

The psychological toll of hostile work environments is an issue throughout medicine, “but it seems greater in certain specialties, and cardiology may be one where it’s more of a problem,” observed Dr. Sen, who studies physician mental health at the University of Michigan, Ann Arbor, and wasn’t associated with the survey.

Mental health concerns in the survey were significantly more common among women than men (33.7% vs 26.3%), and for younger cardiologists, compared with older cardiologists (32.2% for those < 40 vs. 22.1% and 16.8% for those 55-69 and 70 or older, respectively).

Those findings seem to make sense, Dr. Sen observed. “Generally, cardiology and medicine broadly are hierarchical, so being more junior can be stressful.” And if there’s more hostility in the workplace, “it might fall on junior people.”

In other studies, moreover, “a high level of work-family conflict has been a real driver of depression and burnout, and that likely is affecting younger physicians, particularly young women physicians,” who may have smaller children and a greater burden of childcare than their seniors.

He pointed to the survey’s low response rate as an important limitation of the study. Of the 71,022 cardiologists invited to participate, only 5,890 (8.3%) responded and answered the queries on mental health.

With a response rate that low, a survey “can be biased in ways that we can’t predict,” Dr. Sen noted. Also, anyone concerned about the toxicity of their own workplace might be “more likely to respond to the survey than if they worked in a more pleasant place. That would provide a skewed sense of the overall experience of cardiologists.”

Those issues might not be a concern with the current survey, however, “because the results are consistent with other studies with higher response rates.”
 

‘Sobering report’

An accompanying editorial said Dr. Sharm and colleagues have provided “a sobering report on the global prevalence and potential contributors to mental health concerns” in the surveyed population.

Based on its lessons, Andrew J. Sauer, MD, Saint Luke’s Mid America Heart Institute, Kansas City, Mo., proposed several potential “interventions” the field could enact.

It could “selectively promote leaders who strive to mitigate implicit bias, discrimination, and harassment while advancing diversity, equity, and inclusion within the broad ranks of cardiologists.”

Also, he continued, “we must eliminate the stigmatization of mental illness among physicians. We need to handle mental health concerns with compassion and without blaming, like how we strive to treat our veterans who suffer from posttraumatic stress disorder.”

Lastly, Dr. Sauer wrote, “mentorship programs should be formalized to assist the cardiologist in transition zones from early to mid-career, with particular attention to women and those experiencing a simultaneously increased load of family burdens that compound existing workplace contributors to burnout and psychological distress.”
 

Years in practice

Of the cardiologists who responded to the survey’s mental health questions, 28% reported they have experienced mental health issues that could include alcohol/drug use disorder, suicidal tendencies, psychological distress (including anxiety, irritability, or anger), “other psychiatric disorders” (such as panic disorder, posttraumatic stress, or eating disorders) or major psychiatric disorders such as major depression, bipolar disorder, or schizophrenia.

Cardiologists with 5-10 years of practice post-training were more likely than cardiologists practicing for at least 20 years to have mental health concerns (31.9% vs. 22.6%, P < .001).

Mental health concerns were cited by 42% of respondents who cited “any type of discrimination” based on age, sex, race or ethnicity, or sexual orientation, the report noted.

Among those reporting any mental health concern, 2.7% considered suicide within the past year and 2.9% considered suicide more than 12 months previously. Women were more likely than men to consider suicide within the past year (3.8% vs. 2.3%) but were also more likely to seek help (42.3% vs. 31.1%; P < .001 for both differences), the authors wrote.

In multivariate analysis, predictors of mental health concerns included emotional harassment, 2.81 (odds ratio, 2.81; 95% confidence interval, 2.46-3.20), any discrimination (OR, 1.85; 95% CI, 1.61-2.12), being divorced (OR, 1.73; 95% CI, 1.26-2.36, age less than 55 years (OR, 1.43; 95% CI, 1.24-1.66), and being mid-career versus late (OR, 1.36; 95% CI, 1.14-1.62).

Because the survey was conducted from September to October 2019, before the pandemic’s traumatic effects unfolded on health care nearly everywhere, “I think there needs to be a follow-up at some point when everything has leveled out,” Dr. Sharma said. The current study is “a baseline, and not a healthy baseline,” for the field’s state of mental health that has likely grown worse during the pandemic.

But even without such a follow-up, the current study “is actionable enough that it forces us to do something about it right now.”

Dr. Sharma, Dr. Mehta, their coauthors, Dr. Sen, and Dr. Sauer reported no relevant disclosures.

A version of this article first appeared on Medscape.com.

More than a quarter of cardiologists in an international survey reported experiencing mental health conditions ranging from anxiety or anger issues to major depression or other psychiatric disorders.  

Such conditions varied in prevalence by cardiology subspecialty and years in the field, were more common in women than in men, and were closely linked to enduring hostile work environments and other strains of professional life.

The survey, conducted only months before the COVID-19 pandemic and with its share of limitations, still paints a picture that’s not pretty.

For example, mental health concerns were reported by about 42% of respondents who cited a hostile work environment, defined as workplace experience of discrimination based on age, sex, religion, race or ethnicity, or emotional or sexual harassment. Conversely, the prevalence of these concerns reached only 17% among those without such workplace conditions.

The study shows substantial overlap between cardiologists reporting hostility at work and those with mental health concerns, “and that was a significant finding,” Garima Sharma, MD, Johns Hopkins University, Baltimore, said in an interview.

Still, only 31% of male and 42% of female cardiologists (P < .001) reporting mental health concerns also said they had sought professional help either within or outside their own institutions.

That means “there is a lot of silent suffering” in the field, said Dr. Sharma, who is lead author on the study, published in the Journal of the American College of Cardiology.
 

Bringing back the conversation

The survey findings, she added, point to at least two potential ways the cardiology community can strive to diminish what may be a major underlying cause of the mental health concerns and their consequences.

“If you work towards reducing hostility at work and making mental health a priority for your workforce, then those experiencing these types of egregious conditions based on age, gender, race, ethnicity, or sexual orientation are less likely to be harmed.”

Mental health concerns among cardiologists are seldom openly discussed, so the current study can be “a way to bring them back into the conversation,” Dr. Sharma said. Clinician mental health “is extremely important because it directly impacts patient care and productivity.”

The survey’s reported mental health conditions “are an issue across the board in medicine, and amongst our medical students as well,” senior author Laxmi S. Mehta, MD, professor of internal medicine at Ohio State University, Columbus, said in an interview. The current study provides new details about their prevalence and predictors in cardiology and, she hopes, may improve the field’s awareness of and efforts to address the problem.

“We need to support those who have underlying mental health conditions, as well as improve the work environment to reduce contributory factors to mental illnesses. And we also need to work on reducing the stigma associated with seeking treatment and on reducing the barriers to receiving treatment,” said Dr. Mehta, who chairs the Workgroup on Clinician Well-Being of the ACC, which conducted the survey in 2019.
 

A global perspective

Cardiologists in Africa, the Americas, Asia, Europe, the Middle East, and Oceania – 5,890 in all – responded to mental health questions on the survey, which was novel for its global reach and insights across continents and cultures.

Respondents in South America and Central America reported the highest prevalences of mental health concerns, outliers at about 39% and 33%, respectively. Rates for most other geographic regions ranged narrowly from about 20% to 26%, the lowest reported in Asia and the Middle East.

Dr. Sharma acknowledged that the countries probably varied widely in social and cultural factors likely to influence survey responses, such as interpretation of the questionnaire’s mental health terminology or the degree to which the disorders are stigmatized.

“I think it’s hard to say how people may or may not respond culturally to a certain word or metric,” she said. But on the survey results, “whether you’re practicing in rural America, in rural India, or in the United Arab Emirates, Oceania, or Eastern Europe, there is a level of consistency, across the board, in what people are recognizing as mental health conditions.”
 

Junior vs. senior physicians

The global perspective “is a nice positive of the study, and the high rates in Central America and South America I think were something the field was not aware of and are an important contribution,” Srijan Sen, MD, PhD, said in an interview.

The psychological toll of hostile work environments is an issue throughout medicine, “but it seems greater in certain specialties, and cardiology may be one where it’s more of a problem,” observed Dr. Sen, who studies physician mental health at the University of Michigan, Ann Arbor, and wasn’t associated with the survey.

Mental health concerns in the survey were significantly more common among women than men (33.7% vs 26.3%), and for younger cardiologists, compared with older cardiologists (32.2% for those < 40 vs. 22.1% and 16.8% for those 55-69 and 70 or older, respectively).

Those findings seem to make sense, Dr. Sen observed. “Generally, cardiology and medicine broadly are hierarchical, so being more junior can be stressful.” And if there’s more hostility in the workplace, “it might fall on junior people.”

In other studies, moreover, “a high level of work-family conflict has been a real driver of depression and burnout, and that likely is affecting younger physicians, particularly young women physicians,” who may have smaller children and a greater burden of childcare than their seniors.

He pointed to the survey’s low response rate as an important limitation of the study. Of the 71,022 cardiologists invited to participate, only 5,890 (8.3%) responded and answered the queries on mental health.

With a response rate that low, a survey “can be biased in ways that we can’t predict,” Dr. Sen noted. Also, anyone concerned about the toxicity of their own workplace might be “more likely to respond to the survey than if they worked in a more pleasant place. That would provide a skewed sense of the overall experience of cardiologists.”

Those issues might not be a concern with the current survey, however, “because the results are consistent with other studies with higher response rates.”
 

‘Sobering report’

An accompanying editorial said Dr. Sharm and colleagues have provided “a sobering report on the global prevalence and potential contributors to mental health concerns” in the surveyed population.

Based on its lessons, Andrew J. Sauer, MD, Saint Luke’s Mid America Heart Institute, Kansas City, Mo., proposed several potential “interventions” the field could enact.

It could “selectively promote leaders who strive to mitigate implicit bias, discrimination, and harassment while advancing diversity, equity, and inclusion within the broad ranks of cardiologists.”

Also, he continued, “we must eliminate the stigmatization of mental illness among physicians. We need to handle mental health concerns with compassion and without blaming, like how we strive to treat our veterans who suffer from posttraumatic stress disorder.”

Lastly, Dr. Sauer wrote, “mentorship programs should be formalized to assist the cardiologist in transition zones from early to mid-career, with particular attention to women and those experiencing a simultaneously increased load of family burdens that compound existing workplace contributors to burnout and psychological distress.”
 

Years in practice

Of the cardiologists who responded to the survey’s mental health questions, 28% reported they have experienced mental health issues that could include alcohol/drug use disorder, suicidal tendencies, psychological distress (including anxiety, irritability, or anger), “other psychiatric disorders” (such as panic disorder, posttraumatic stress, or eating disorders) or major psychiatric disorders such as major depression, bipolar disorder, or schizophrenia.

Cardiologists with 5-10 years of practice post-training were more likely than cardiologists practicing for at least 20 years to have mental health concerns (31.9% vs. 22.6%, P < .001).

Mental health concerns were cited by 42% of respondents who cited “any type of discrimination” based on age, sex, race or ethnicity, or sexual orientation, the report noted.

Among those reporting any mental health concern, 2.7% considered suicide within the past year and 2.9% considered suicide more than 12 months previously. Women were more likely than men to consider suicide within the past year (3.8% vs. 2.3%) but were also more likely to seek help (42.3% vs. 31.1%; P < .001 for both differences), the authors wrote.

In multivariate analysis, predictors of mental health concerns included emotional harassment, 2.81 (odds ratio, 2.81; 95% confidence interval, 2.46-3.20), any discrimination (OR, 1.85; 95% CI, 1.61-2.12), being divorced (OR, 1.73; 95% CI, 1.26-2.36, age less than 55 years (OR, 1.43; 95% CI, 1.24-1.66), and being mid-career versus late (OR, 1.36; 95% CI, 1.14-1.62).

Because the survey was conducted from September to October 2019, before the pandemic’s traumatic effects unfolded on health care nearly everywhere, “I think there needs to be a follow-up at some point when everything has leveled out,” Dr. Sharma said. The current study is “a baseline, and not a healthy baseline,” for the field’s state of mental health that has likely grown worse during the pandemic.

But even without such a follow-up, the current study “is actionable enough that it forces us to do something about it right now.”

Dr. Sharma, Dr. Mehta, their coauthors, Dr. Sen, and Dr. Sauer reported no relevant disclosures.

A version of this article first appeared on Medscape.com.

More than a quarter of cardiologists in an international survey reported experiencing mental health conditions ranging from anxiety or anger issues to major depression or other psychiatric disorders.  

Such conditions varied in prevalence by cardiology subspecialty and years in the field, were more common in women than in men, and were closely linked to enduring hostile work environments and other strains of professional life.

The survey, conducted only months before the COVID-19 pandemic and with its share of limitations, still paints a picture that’s not pretty.

For example, mental health concerns were reported by about 42% of respondents who cited a hostile work environment, defined as workplace experience of discrimination based on age, sex, religion, race or ethnicity, or emotional or sexual harassment. Conversely, the prevalence of these concerns reached only 17% among those without such workplace conditions.

The study shows substantial overlap between cardiologists reporting hostility at work and those with mental health concerns, “and that was a significant finding,” Garima Sharma, MD, Johns Hopkins University, Baltimore, said in an interview.

Still, only 31% of male and 42% of female cardiologists (P < .001) reporting mental health concerns also said they had sought professional help either within or outside their own institutions.

That means “there is a lot of silent suffering” in the field, said Dr. Sharma, who is lead author on the study, published in the Journal of the American College of Cardiology.
 

Bringing back the conversation

The survey findings, she added, point to at least two potential ways the cardiology community can strive to diminish what may be a major underlying cause of the mental health concerns and their consequences.

“If you work towards reducing hostility at work and making mental health a priority for your workforce, then those experiencing these types of egregious conditions based on age, gender, race, ethnicity, or sexual orientation are less likely to be harmed.”

Mental health concerns among cardiologists are seldom openly discussed, so the current study can be “a way to bring them back into the conversation,” Dr. Sharma said. Clinician mental health “is extremely important because it directly impacts patient care and productivity.”

The survey’s reported mental health conditions “are an issue across the board in medicine, and amongst our medical students as well,” senior author Laxmi S. Mehta, MD, professor of internal medicine at Ohio State University, Columbus, said in an interview. The current study provides new details about their prevalence and predictors in cardiology and, she hopes, may improve the field’s awareness of and efforts to address the problem.

“We need to support those who have underlying mental health conditions, as well as improve the work environment to reduce contributory factors to mental illnesses. And we also need to work on reducing the stigma associated with seeking treatment and on reducing the barriers to receiving treatment,” said Dr. Mehta, who chairs the Workgroup on Clinician Well-Being of the ACC, which conducted the survey in 2019.
 

A global perspective

Cardiologists in Africa, the Americas, Asia, Europe, the Middle East, and Oceania – 5,890 in all – responded to mental health questions on the survey, which was novel for its global reach and insights across continents and cultures.

Respondents in South America and Central America reported the highest prevalences of mental health concerns, outliers at about 39% and 33%, respectively. Rates for most other geographic regions ranged narrowly from about 20% to 26%, the lowest reported in Asia and the Middle East.

Dr. Sharma acknowledged that the countries probably varied widely in social and cultural factors likely to influence survey responses, such as interpretation of the questionnaire’s mental health terminology or the degree to which the disorders are stigmatized.

“I think it’s hard to say how people may or may not respond culturally to a certain word or metric,” she said. But on the survey results, “whether you’re practicing in rural America, in rural India, or in the United Arab Emirates, Oceania, or Eastern Europe, there is a level of consistency, across the board, in what people are recognizing as mental health conditions.”
 

Junior vs. senior physicians

The global perspective “is a nice positive of the study, and the high rates in Central America and South America I think were something the field was not aware of and are an important contribution,” Srijan Sen, MD, PhD, said in an interview.

The psychological toll of hostile work environments is an issue throughout medicine, “but it seems greater in certain specialties, and cardiology may be one where it’s more of a problem,” observed Dr. Sen, who studies physician mental health at the University of Michigan, Ann Arbor, and wasn’t associated with the survey.

Mental health concerns in the survey were significantly more common among women than men (33.7% vs 26.3%), and for younger cardiologists, compared with older cardiologists (32.2% for those < 40 vs. 22.1% and 16.8% for those 55-69 and 70 or older, respectively).

Those findings seem to make sense, Dr. Sen observed. “Generally, cardiology and medicine broadly are hierarchical, so being more junior can be stressful.” And if there’s more hostility in the workplace, “it might fall on junior people.”

In other studies, moreover, “a high level of work-family conflict has been a real driver of depression and burnout, and that likely is affecting younger physicians, particularly young women physicians,” who may have smaller children and a greater burden of childcare than their seniors.

He pointed to the survey’s low response rate as an important limitation of the study. Of the 71,022 cardiologists invited to participate, only 5,890 (8.3%) responded and answered the queries on mental health.

With a response rate that low, a survey “can be biased in ways that we can’t predict,” Dr. Sen noted. Also, anyone concerned about the toxicity of their own workplace might be “more likely to respond to the survey than if they worked in a more pleasant place. That would provide a skewed sense of the overall experience of cardiologists.”

Those issues might not be a concern with the current survey, however, “because the results are consistent with other studies with higher response rates.”
 

‘Sobering report’

An accompanying editorial said Dr. Sharm and colleagues have provided “a sobering report on the global prevalence and potential contributors to mental health concerns” in the surveyed population.

Based on its lessons, Andrew J. Sauer, MD, Saint Luke’s Mid America Heart Institute, Kansas City, Mo., proposed several potential “interventions” the field could enact.

It could “selectively promote leaders who strive to mitigate implicit bias, discrimination, and harassment while advancing diversity, equity, and inclusion within the broad ranks of cardiologists.”

Also, he continued, “we must eliminate the stigmatization of mental illness among physicians. We need to handle mental health concerns with compassion and without blaming, like how we strive to treat our veterans who suffer from posttraumatic stress disorder.”

Lastly, Dr. Sauer wrote, “mentorship programs should be formalized to assist the cardiologist in transition zones from early to mid-career, with particular attention to women and those experiencing a simultaneously increased load of family burdens that compound existing workplace contributors to burnout and psychological distress.”
 

Years in practice

Of the cardiologists who responded to the survey’s mental health questions, 28% reported they have experienced mental health issues that could include alcohol/drug use disorder, suicidal tendencies, psychological distress (including anxiety, irritability, or anger), “other psychiatric disorders” (such as panic disorder, posttraumatic stress, or eating disorders) or major psychiatric disorders such as major depression, bipolar disorder, or schizophrenia.

Cardiologists with 5-10 years of practice post-training were more likely than cardiologists practicing for at least 20 years to have mental health concerns (31.9% vs. 22.6%, P < .001).

Mental health concerns were cited by 42% of respondents who cited “any type of discrimination” based on age, sex, race or ethnicity, or sexual orientation, the report noted.

Among those reporting any mental health concern, 2.7% considered suicide within the past year and 2.9% considered suicide more than 12 months previously. Women were more likely than men to consider suicide within the past year (3.8% vs. 2.3%) but were also more likely to seek help (42.3% vs. 31.1%; P < .001 for both differences), the authors wrote.

In multivariate analysis, predictors of mental health concerns included emotional harassment, 2.81 (odds ratio, 2.81; 95% confidence interval, 2.46-3.20), any discrimination (OR, 1.85; 95% CI, 1.61-2.12), being divorced (OR, 1.73; 95% CI, 1.26-2.36, age less than 55 years (OR, 1.43; 95% CI, 1.24-1.66), and being mid-career versus late (OR, 1.36; 95% CI, 1.14-1.62).

Because the survey was conducted from September to October 2019, before the pandemic’s traumatic effects unfolded on health care nearly everywhere, “I think there needs to be a follow-up at some point when everything has leveled out,” Dr. Sharma said. The current study is “a baseline, and not a healthy baseline,” for the field’s state of mental health that has likely grown worse during the pandemic.

But even without such a follow-up, the current study “is actionable enough that it forces us to do something about it right now.”

Dr. Sharma, Dr. Mehta, their coauthors, Dr. Sen, and Dr. Sauer reported no relevant disclosures.

A version of this article first appeared on Medscape.com.

Nine top professional emergency medicine organizations in the United States jointly issued a letter expressing concerns about the misleading and incomplete nature of a systematic review issued by the Agency for Healthcare Research and Quality on diagnostic errors in the emergency department.

The AHRQ review, issued on Dec. 15, 2022, stated that the findings of their study translate “to about 1 in 18 emergency department patients receiving an incorrect diagnosis, 1 in 50 suffering an adverse event, and 1 in 350 suffering permanent disability or death.” The authors describe these rates as similar to those seen in primary care and inpatient hospital settings.

The review was conducted through an Evidence-Based Practice Center as part of AHRQ’s Effective Health Care Program. The authors included data from 279 studies in the review. They identified the five most frequently misdiagnosed conditions in the ED as stroke, MI, aortic aneurysm and dissection, spinal cord compression and injury, and venous thromboembolism.

The authors noted that, given an estimated 130 million ED visits in the United States each year, the overall rate of incorrect diagnoses in the ED is approximately 5.7% and that 2.0% of the patients whose conditions were misdiagnosed suffer an adverse event as a result. On a local level, the authors estimate that an average ED with approximately 25,000 visits per year could experience 1,400 diagnostic errors, 500 diagnostic adverse events, and 75 serious harms, including 50 deaths. However, the authors noted that the overall error and harm rates were based on three studies from outside the United States (Canada, Spain, and Switzerland) and that only two of these were used to estimate harms.

“It’s imperative that we, as emergency physicians, inform the public that the AHRQ report used flawed methodology and statistics that extrapolated – and therefore overstated – the potential for harm when receiving care in US emergency departments,” Robert Glatter, MD, an emergency medicine physician at Lenox Hill Hospital at Northwell Health and an assistant professor at Hofstra University, Hempstead, N.Y., said in an interview.
 

Emergency medicine organizations express concerns for accuracy

The American College of Emergency Physicians and eight other medical organizations representing emergency medicine in the United States sent a letter to the AHRQ on Dec. 14, 2022, spelling out their concerns. The review was conducted as part of the AHRQ’s ongoing Effective Health Care Program, and the organizations had the opportunity to review a draft before it was published. On reading the review, they asked that the publication of the review be delayed. “After reviewing the executive summary and initial draft, we believe that the report makes misleading, incomplete, and erroneous conclusions from the literature reviewed and conveys a tone that inaccurately characterizes and unnecessarily disparages the practice of emergency medicine in the United States,” the organizations wrote in their letter.

The concerns of the emergency medicine organizations fell into four categories: misrepresentation of the practice and nature of emergency medicine; applicability of references cited; inaccurate interpretation of malpractice data; and the reporting of a single overall diagnostic error rate of 5.7% in EDs.

The practice of emergency medicine is variable and unique among specialties in that the focus is less about the final diagnosis and more about immediate identification and treatment of life-threatening conditions, according to the letter.

Notably, many of the studies cited did not mention whether the patient’s final diagnosis was apparent on admission to the ED. “Without this knowledge, it is completely inappropriate to label such discrepancies as ‘ED diagnostic error,’ ” the organizations wrote.

All medical specialties have room for improvement, but the current AHRQ review appears not to identify these opportunities, and instead of contributing to a discussion of improving patient care in the ED, it may cause harm by presenting misinformation, they said.
 

Misleading and inadequate evidence

“I strongly agree with the concerns mentioned from ACEP and other key organizations about the problems and conclusions reached in the AHRQ report,” Dr. Glatter said in an interview.

“The methodology used to arrive at the conclusions [in the review] was flawed and does not provide an accurate estimate of diagnostic error and, consequently, misdiagnosis and deaths occurring in emergency departments in the U.S.,” he said. “The startling headline that 250,000 people die annually in U.S. EDs was extrapolated from a single study based on one death that occurred in a Canadian ED in 2004,” Dr. Glatter noted. “Clearly, this is not only poor methodology but flawed science.”

The AHRQ report misused one death from this single study to estimate the death rate across the United States, Dr. Glatter explained, and this overestimate improperly inflated and magnified the number of potential patients that may have been harmed by physician error.

“This flawed evidence would actually place ED misdiagnoses in the top five causes of death in the United States, with 1 in every 500 ED patients dying as a result of an error by a physician. Simply put, there is just no evidence to support such a claim,” said Dr. Glatter.

The repercussions of the AHRQ review could be harmful to patients by instilling fear and doubt about the ability of emergency physicians to diagnose those who present with life-threatening conditions, Dr. Glatter said.

“This more balanced and accurate picture of the role of emergency physicians in diagnosing and managing such emergencies needs to be communicated to the public in order to reassure and instill confidence in our role in the sequence of emergency care in relation to continuity of care in patients presenting to the ED,” he said.

“While our primary role as emergency medicine physicians is to stabilize and evaluate patients, arriving at a particular diagnosis is not always possible for some conditions,” and additional diagnostic testing is often needed to identify more specific causes of symptoms, Dr. Glatter added.

Additional research is needed for a more accurate representation of diagnostic errors in the ED, said Dr. Glatter. New prospective studies are needed to address outcomes in U.S. EDs that account for the latest advances and diagnostic modalities in emergency medicine, “particularly advances in bedside ultrasound that can expedite critical decision-making, which can be lifesaving.

“The AHRQ report is simply not an accurate reflection of the technology and skill set that current emergency medicine practice offers our patients in 2023.”

Dr. Glatter disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Nine top professional emergency medicine organizations in the United States jointly issued a letter expressing concerns about the misleading and incomplete nature of a systematic review issued by the Agency for Healthcare Research and Quality on diagnostic errors in the emergency department.

The AHRQ review, issued on Dec. 15, 2022, stated that the findings of their study translate “to about 1 in 18 emergency department patients receiving an incorrect diagnosis, 1 in 50 suffering an adverse event, and 1 in 350 suffering permanent disability or death.” The authors describe these rates as similar to those seen in primary care and inpatient hospital settings.

The review was conducted through an Evidence-Based Practice Center as part of AHRQ’s Effective Health Care Program. The authors included data from 279 studies in the review. They identified the five most frequently misdiagnosed conditions in the ED as stroke, MI, aortic aneurysm and dissection, spinal cord compression and injury, and venous thromboembolism.

The authors noted that, given an estimated 130 million ED visits in the United States each year, the overall rate of incorrect diagnoses in the ED is approximately 5.7% and that 2.0% of the patients whose conditions were misdiagnosed suffer an adverse event as a result. On a local level, the authors estimate that an average ED with approximately 25,000 visits per year could experience 1,400 diagnostic errors, 500 diagnostic adverse events, and 75 serious harms, including 50 deaths. However, the authors noted that the overall error and harm rates were based on three studies from outside the United States (Canada, Spain, and Switzerland) and that only two of these were used to estimate harms.

“It’s imperative that we, as emergency physicians, inform the public that the AHRQ report used flawed methodology and statistics that extrapolated – and therefore overstated – the potential for harm when receiving care in US emergency departments,” Robert Glatter, MD, an emergency medicine physician at Lenox Hill Hospital at Northwell Health and an assistant professor at Hofstra University, Hempstead, N.Y., said in an interview.
 

Emergency medicine organizations express concerns for accuracy

The American College of Emergency Physicians and eight other medical organizations representing emergency medicine in the United States sent a letter to the AHRQ on Dec. 14, 2022, spelling out their concerns. The review was conducted as part of the AHRQ’s ongoing Effective Health Care Program, and the organizations had the opportunity to review a draft before it was published. On reading the review, they asked that the publication of the review be delayed. “After reviewing the executive summary and initial draft, we believe that the report makes misleading, incomplete, and erroneous conclusions from the literature reviewed and conveys a tone that inaccurately characterizes and unnecessarily disparages the practice of emergency medicine in the United States,” the organizations wrote in their letter.

The concerns of the emergency medicine organizations fell into four categories: misrepresentation of the practice and nature of emergency medicine; applicability of references cited; inaccurate interpretation of malpractice data; and the reporting of a single overall diagnostic error rate of 5.7% in EDs.

The practice of emergency medicine is variable and unique among specialties in that the focus is less about the final diagnosis and more about immediate identification and treatment of life-threatening conditions, according to the letter.

Notably, many of the studies cited did not mention whether the patient’s final diagnosis was apparent on admission to the ED. “Without this knowledge, it is completely inappropriate to label such discrepancies as ‘ED diagnostic error,’ ” the organizations wrote.

All medical specialties have room for improvement, but the current AHRQ review appears not to identify these opportunities, and instead of contributing to a discussion of improving patient care in the ED, it may cause harm by presenting misinformation, they said.
 

Misleading and inadequate evidence

“I strongly agree with the concerns mentioned from ACEP and other key organizations about the problems and conclusions reached in the AHRQ report,” Dr. Glatter said in an interview.

“The methodology used to arrive at the conclusions [in the review] was flawed and does not provide an accurate estimate of diagnostic error and, consequently, misdiagnosis and deaths occurring in emergency departments in the U.S.,” he said. “The startling headline that 250,000 people die annually in U.S. EDs was extrapolated from a single study based on one death that occurred in a Canadian ED in 2004,” Dr. Glatter noted. “Clearly, this is not only poor methodology but flawed science.”

The AHRQ report misused one death from this single study to estimate the death rate across the United States, Dr. Glatter explained, and this overestimate improperly inflated and magnified the number of potential patients that may have been harmed by physician error.

“This flawed evidence would actually place ED misdiagnoses in the top five causes of death in the United States, with 1 in every 500 ED patients dying as a result of an error by a physician. Simply put, there is just no evidence to support such a claim,” said Dr. Glatter.

The repercussions of the AHRQ review could be harmful to patients by instilling fear and doubt about the ability of emergency physicians to diagnose those who present with life-threatening conditions, Dr. Glatter said.

“This more balanced and accurate picture of the role of emergency physicians in diagnosing and managing such emergencies needs to be communicated to the public in order to reassure and instill confidence in our role in the sequence of emergency care in relation to continuity of care in patients presenting to the ED,” he said.

“While our primary role as emergency medicine physicians is to stabilize and evaluate patients, arriving at a particular diagnosis is not always possible for some conditions,” and additional diagnostic testing is often needed to identify more specific causes of symptoms, Dr. Glatter added.

Additional research is needed for a more accurate representation of diagnostic errors in the ED, said Dr. Glatter. New prospective studies are needed to address outcomes in U.S. EDs that account for the latest advances and diagnostic modalities in emergency medicine, “particularly advances in bedside ultrasound that can expedite critical decision-making, which can be lifesaving.

“The AHRQ report is simply not an accurate reflection of the technology and skill set that current emergency medicine practice offers our patients in 2023.”

Dr. Glatter disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Nine top professional emergency medicine organizations in the United States jointly issued a letter expressing concerns about the misleading and incomplete nature of a systematic review issued by the Agency for Healthcare Research and Quality on diagnostic errors in the emergency department.

The AHRQ review, issued on Dec. 15, 2022, stated that the findings of their study translate “to about 1 in 18 emergency department patients receiving an incorrect diagnosis, 1 in 50 suffering an adverse event, and 1 in 350 suffering permanent disability or death.” The authors describe these rates as similar to those seen in primary care and inpatient hospital settings.

The review was conducted through an Evidence-Based Practice Center as part of AHRQ’s Effective Health Care Program. The authors included data from 279 studies in the review. They identified the five most frequently misdiagnosed conditions in the ED as stroke, MI, aortic aneurysm and dissection, spinal cord compression and injury, and venous thromboembolism.

The authors noted that, given an estimated 130 million ED visits in the United States each year, the overall rate of incorrect diagnoses in the ED is approximately 5.7% and that 2.0% of the patients whose conditions were misdiagnosed suffer an adverse event as a result. On a local level, the authors estimate that an average ED with approximately 25,000 visits per year could experience 1,400 diagnostic errors, 500 diagnostic adverse events, and 75 serious harms, including 50 deaths. However, the authors noted that the overall error and harm rates were based on three studies from outside the United States (Canada, Spain, and Switzerland) and that only two of these were used to estimate harms.

“It’s imperative that we, as emergency physicians, inform the public that the AHRQ report used flawed methodology and statistics that extrapolated – and therefore overstated – the potential for harm when receiving care in US emergency departments,” Robert Glatter, MD, an emergency medicine physician at Lenox Hill Hospital at Northwell Health and an assistant professor at Hofstra University, Hempstead, N.Y., said in an interview.
 

Emergency medicine organizations express concerns for accuracy

The American College of Emergency Physicians and eight other medical organizations representing emergency medicine in the United States sent a letter to the AHRQ on Dec. 14, 2022, spelling out their concerns. The review was conducted as part of the AHRQ’s ongoing Effective Health Care Program, and the organizations had the opportunity to review a draft before it was published. On reading the review, they asked that the publication of the review be delayed. “After reviewing the executive summary and initial draft, we believe that the report makes misleading, incomplete, and erroneous conclusions from the literature reviewed and conveys a tone that inaccurately characterizes and unnecessarily disparages the practice of emergency medicine in the United States,” the organizations wrote in their letter.

The concerns of the emergency medicine organizations fell into four categories: misrepresentation of the practice and nature of emergency medicine; applicability of references cited; inaccurate interpretation of malpractice data; and the reporting of a single overall diagnostic error rate of 5.7% in EDs.

The practice of emergency medicine is variable and unique among specialties in that the focus is less about the final diagnosis and more about immediate identification and treatment of life-threatening conditions, according to the letter.

Notably, many of the studies cited did not mention whether the patient’s final diagnosis was apparent on admission to the ED. “Without this knowledge, it is completely inappropriate to label such discrepancies as ‘ED diagnostic error,’ ” the organizations wrote.

All medical specialties have room for improvement, but the current AHRQ review appears not to identify these opportunities, and instead of contributing to a discussion of improving patient care in the ED, it may cause harm by presenting misinformation, they said.
 

Misleading and inadequate evidence

“I strongly agree with the concerns mentioned from ACEP and other key organizations about the problems and conclusions reached in the AHRQ report,” Dr. Glatter said in an interview.

“The methodology used to arrive at the conclusions [in the review] was flawed and does not provide an accurate estimate of diagnostic error and, consequently, misdiagnosis and deaths occurring in emergency departments in the U.S.,” he said. “The startling headline that 250,000 people die annually in U.S. EDs was extrapolated from a single study based on one death that occurred in a Canadian ED in 2004,” Dr. Glatter noted. “Clearly, this is not only poor methodology but flawed science.”

The AHRQ report misused one death from this single study to estimate the death rate across the United States, Dr. Glatter explained, and this overestimate improperly inflated and magnified the number of potential patients that may have been harmed by physician error.

“This flawed evidence would actually place ED misdiagnoses in the top five causes of death in the United States, with 1 in every 500 ED patients dying as a result of an error by a physician. Simply put, there is just no evidence to support such a claim,” said Dr. Glatter.

The repercussions of the AHRQ review could be harmful to patients by instilling fear and doubt about the ability of emergency physicians to diagnose those who present with life-threatening conditions, Dr. Glatter said.

“This more balanced and accurate picture of the role of emergency physicians in diagnosing and managing such emergencies needs to be communicated to the public in order to reassure and instill confidence in our role in the sequence of emergency care in relation to continuity of care in patients presenting to the ED,” he said.

“While our primary role as emergency medicine physicians is to stabilize and evaluate patients, arriving at a particular diagnosis is not always possible for some conditions,” and additional diagnostic testing is often needed to identify more specific causes of symptoms, Dr. Glatter added.

Additional research is needed for a more accurate representation of diagnostic errors in the ED, said Dr. Glatter. New prospective studies are needed to address outcomes in U.S. EDs that account for the latest advances and diagnostic modalities in emergency medicine, “particularly advances in bedside ultrasound that can expedite critical decision-making, which can be lifesaving.

“The AHRQ report is simply not an accurate reflection of the technology and skill set that current emergency medicine practice offers our patients in 2023.”

Dr. Glatter disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

With no proven treatments for long COVID, millions of Americans struggling with debilitating symptoms may be wondering whether it’s worth it to try something they’ve never considered before: a clinical trial. 

Dozens of clinical trials nationwide are already underway or starting soon, many of which are aided by $1.5 billion in funding from the National Institutes of Health to help identify new treatments for common symptoms like brain fog, fatigue, sleep disturbances, and a hard time breathing. But it may take years for these trials to prove which drugs, devices, and behavioral therapies are safe and effective. 

“We’re not in warp speed,” said Kanecia Zimmerman, MD, a principal investigator at the Duke Clinical Research Institute in Durham, N.C., who is overseeing long COVID trials for the NIH. Operation Warp Speed – the 2020-2021 federal effort to get COVID vaccines designed, tested, authorized and distributed – benefited from existing scientific knowledge about other coronaviruses and about vaccines in general. But there’s no similar foundation of scientific knowledge about long COVID. 

“We are in a place of not really knowing anything,” Dr. Zimmerman said.

But some glimmers of hope are emerging. A Veterans Affairs study recently found the antiviral Paxlovid might help prevent long COVID. A small case study at Yale found the ADHD drug guanfacine may ease brain fog from long COVID. And preliminary results from an NIH-funded study suggest COVID vaccines might help children with a rare but serious inflammatory condition known as multisystem inflammatory syndrome (MIS-C). 

More results are expected very soon from the trial for kids with MIS-C, which can strike suddenly long after a COVID infection clears up. While the exact causes aren’t yet clear, MIS-C can cause dangerous inflammation in the heart, lungs, kidneys, brain, skin, eyes, or gastrointestinal system. 

Because the virus often triggered a delayed response of MIS-C in kids who had few if any symptoms of acute COVID-19, scientists wondered whether children infected with the virus might respond to a vaccine dose to prevent MIS-C from developing, Gary Gibbons, MD, director of the National Heart, Lung, and Blood Institute, said during a Dec. 9 presentation at the NIH. It’s not yet clear if vaccination helps, but it doesn’t harm the children, Dr. Gibbons said. 

“Indeed, the studies suggest with some relief that yes, these children could be vaccinated safely,” he said. 

Several new trials are also testing Paxlovid against long COVID, including one late-stage study that may have results in about a year. 

“We already know that Paxlovid reduces the risk of developing long COVID, but it would be a game changer if it can improve long COVID symptoms as well,” said Surendra Barshikar, MD, an associate professor and medical director of the COVID Recover program at the University of Texas Southwestern Medical Center, Dallas. 

In other studies, researchers are looking at a wide variety of previously approved and experimental drugs and devices. For example, scientists in New York are testing the mood stabilizer lithium to treat brain fog and fatigue. And researchers in Illinois are investigating efgartigimod, a drug approved for the rare muscle-weakening autoimmune disorder myasthenia gravis, to see if it helps ease a long COVID complication known as POTS that can cause a sudden rapid heart rate and chronic fatigue. 

“The good news is that enrollment will proceed quickly, given the vast number of patients,” said Kristin Englund, MD, director of the reCOVer Center of Excellence at the Cleveland Clinic. 

This is all encouraging because roughly one in five American adults who have acute COVID infections develop persistent symptoms of long COVID, also known as post–acute sequelae of SARS-CoV-2 (PASC). And many of these long COVID patients have complex, overlapping clusters of symptoms that make traditional treatment approaches largely ineffective against this new, formidable disease. 

But not every patient living with long COVID will qualify for trials or find it easy to take part even if they do. Patients should consider how severe their symptoms are, the potential risks of any experimental treatments, and the many challenges they may have with getting to and from clinical trial sites that are largely concentrated around major cities and might be far from home. 

While this holds true for any type of trial, it’s essential for long COVID patients, who may have fatigue, muscle weakness, and other symptoms that make distance an impossible factor to ignore, said Aaron Friedberg, MD, clinical colead of the post–COVID-19 recovery program at the Ohio State University Wexner Medical Center, Columbus. 

“I think it is a personal decision, since the fatigue and pain that patients with PASC can experience can make it very challenging to travel long distances,” Dr. Friedberg said. “I would recommend calling or messaging ahead to find out exactly what type of travel might be required because there may be steps that can be completed by email or video, which could make it easier to participate, and some trials may be entirely remote.”

Even when patients feel up to the travel, they still might not be a good fit for a clinical trial. Scientists often look for people who didn’t have pre-existing health problems before they got long COVID, Dr. Barshikar noted. Patients taking medications may also be unable to participate in drug trials, particularly for experimental treatments because of concerns about unknown side effects from drug interactions. 

When clinical trials do seem like a good option, patients may want to consider seeking treatment at an academic medical center that is already doing long COVID research, particularly if their symptoms are too complex or severe to manage only through their primary care provider, said Jonathan Whiteson, MD, who helped draft long COVID treatment guidelines for the American Academy of Physical Medicine and Rehabilitation. He also serves as codirector of the New York University Langone Health post–COVID care program.

Many health care professionals on the front lines treating long COVID patients are optimistic that the sheer number of trials and the vast number of patients taking part should ultimately produce some better treatment options than people have right now. It’s just not going to happen overnight. 

“I suspect that while we will see some new treatments coming in the next 1-2 years, it may be several years before targets can be identified and full trials conducted to see results,” Dr. Friedberg said. “Getting good data takes time.”

A version of this article first appeared on WebMD.com.

With no proven treatments for long COVID, millions of Americans struggling with debilitating symptoms may be wondering whether it’s worth it to try something they’ve never considered before: a clinical trial. 

Dozens of clinical trials nationwide are already underway or starting soon, many of which are aided by $1.5 billion in funding from the National Institutes of Health to help identify new treatments for common symptoms like brain fog, fatigue, sleep disturbances, and a hard time breathing. But it may take years for these trials to prove which drugs, devices, and behavioral therapies are safe and effective. 

“We’re not in warp speed,” said Kanecia Zimmerman, MD, a principal investigator at the Duke Clinical Research Institute in Durham, N.C., who is overseeing long COVID trials for the NIH. Operation Warp Speed – the 2020-2021 federal effort to get COVID vaccines designed, tested, authorized and distributed – benefited from existing scientific knowledge about other coronaviruses and about vaccines in general. But there’s no similar foundation of scientific knowledge about long COVID. 

“We are in a place of not really knowing anything,” Dr. Zimmerman said.

But some glimmers of hope are emerging. A Veterans Affairs study recently found the antiviral Paxlovid might help prevent long COVID. A small case study at Yale found the ADHD drug guanfacine may ease brain fog from long COVID. And preliminary results from an NIH-funded study suggest COVID vaccines might help children with a rare but serious inflammatory condition known as multisystem inflammatory syndrome (MIS-C). 

More results are expected very soon from the trial for kids with MIS-C, which can strike suddenly long after a COVID infection clears up. While the exact causes aren’t yet clear, MIS-C can cause dangerous inflammation in the heart, lungs, kidneys, brain, skin, eyes, or gastrointestinal system. 

Because the virus often triggered a delayed response of MIS-C in kids who had few if any symptoms of acute COVID-19, scientists wondered whether children infected with the virus might respond to a vaccine dose to prevent MIS-C from developing, Gary Gibbons, MD, director of the National Heart, Lung, and Blood Institute, said during a Dec. 9 presentation at the NIH. It’s not yet clear if vaccination helps, but it doesn’t harm the children, Dr. Gibbons said. 

“Indeed, the studies suggest with some relief that yes, these children could be vaccinated safely,” he said. 

Several new trials are also testing Paxlovid against long COVID, including one late-stage study that may have results in about a year. 

“We already know that Paxlovid reduces the risk of developing long COVID, but it would be a game changer if it can improve long COVID symptoms as well,” said Surendra Barshikar, MD, an associate professor and medical director of the COVID Recover program at the University of Texas Southwestern Medical Center, Dallas. 

In other studies, researchers are looking at a wide variety of previously approved and experimental drugs and devices. For example, scientists in New York are testing the mood stabilizer lithium to treat brain fog and fatigue. And researchers in Illinois are investigating efgartigimod, a drug approved for the rare muscle-weakening autoimmune disorder myasthenia gravis, to see if it helps ease a long COVID complication known as POTS that can cause a sudden rapid heart rate and chronic fatigue. 

“The good news is that enrollment will proceed quickly, given the vast number of patients,” said Kristin Englund, MD, director of the reCOVer Center of Excellence at the Cleveland Clinic. 

This is all encouraging because roughly one in five American adults who have acute COVID infections develop persistent symptoms of long COVID, also known as post–acute sequelae of SARS-CoV-2 (PASC). And many of these long COVID patients have complex, overlapping clusters of symptoms that make traditional treatment approaches largely ineffective against this new, formidable disease. 

But not every patient living with long COVID will qualify for trials or find it easy to take part even if they do. Patients should consider how severe their symptoms are, the potential risks of any experimental treatments, and the many challenges they may have with getting to and from clinical trial sites that are largely concentrated around major cities and might be far from home. 

While this holds true for any type of trial, it’s essential for long COVID patients, who may have fatigue, muscle weakness, and other symptoms that make distance an impossible factor to ignore, said Aaron Friedberg, MD, clinical colead of the post–COVID-19 recovery program at the Ohio State University Wexner Medical Center, Columbus. 

“I think it is a personal decision, since the fatigue and pain that patients with PASC can experience can make it very challenging to travel long distances,” Dr. Friedberg said. “I would recommend calling or messaging ahead to find out exactly what type of travel might be required because there may be steps that can be completed by email or video, which could make it easier to participate, and some trials may be entirely remote.”

Even when patients feel up to the travel, they still might not be a good fit for a clinical trial. Scientists often look for people who didn’t have pre-existing health problems before they got long COVID, Dr. Barshikar noted. Patients taking medications may also be unable to participate in drug trials, particularly for experimental treatments because of concerns about unknown side effects from drug interactions. 

When clinical trials do seem like a good option, patients may want to consider seeking treatment at an academic medical center that is already doing long COVID research, particularly if their symptoms are too complex or severe to manage only through their primary care provider, said Jonathan Whiteson, MD, who helped draft long COVID treatment guidelines for the American Academy of Physical Medicine and Rehabilitation. He also serves as codirector of the New York University Langone Health post–COVID care program.

Many health care professionals on the front lines treating long COVID patients are optimistic that the sheer number of trials and the vast number of patients taking part should ultimately produce some better treatment options than people have right now. It’s just not going to happen overnight. 

“I suspect that while we will see some new treatments coming in the next 1-2 years, it may be several years before targets can be identified and full trials conducted to see results,” Dr. Friedberg said. “Getting good data takes time.”

A version of this article first appeared on WebMD.com.

With no proven treatments for long COVID, millions of Americans struggling with debilitating symptoms may be wondering whether it’s worth it to try something they’ve never considered before: a clinical trial. 

Dozens of clinical trials nationwide are already underway or starting soon, many of which are aided by $1.5 billion in funding from the National Institutes of Health to help identify new treatments for common symptoms like brain fog, fatigue, sleep disturbances, and a hard time breathing. But it may take years for these trials to prove which drugs, devices, and behavioral therapies are safe and effective. 

“We’re not in warp speed,” said Kanecia Zimmerman, MD, a principal investigator at the Duke Clinical Research Institute in Durham, N.C., who is overseeing long COVID trials for the NIH. Operation Warp Speed – the 2020-2021 federal effort to get COVID vaccines designed, tested, authorized and distributed – benefited from existing scientific knowledge about other coronaviruses and about vaccines in general. But there’s no similar foundation of scientific knowledge about long COVID. 

“We are in a place of not really knowing anything,” Dr. Zimmerman said.

But some glimmers of hope are emerging. A Veterans Affairs study recently found the antiviral Paxlovid might help prevent long COVID. A small case study at Yale found the ADHD drug guanfacine may ease brain fog from long COVID. And preliminary results from an NIH-funded study suggest COVID vaccines might help children with a rare but serious inflammatory condition known as multisystem inflammatory syndrome (MIS-C). 

More results are expected very soon from the trial for kids with MIS-C, which can strike suddenly long after a COVID infection clears up. While the exact causes aren’t yet clear, MIS-C can cause dangerous inflammation in the heart, lungs, kidneys, brain, skin, eyes, or gastrointestinal system. 

Because the virus often triggered a delayed response of MIS-C in kids who had few if any symptoms of acute COVID-19, scientists wondered whether children infected with the virus might respond to a vaccine dose to prevent MIS-C from developing, Gary Gibbons, MD, director of the National Heart, Lung, and Blood Institute, said during a Dec. 9 presentation at the NIH. It’s not yet clear if vaccination helps, but it doesn’t harm the children, Dr. Gibbons said. 

“Indeed, the studies suggest with some relief that yes, these children could be vaccinated safely,” he said. 

Several new trials are also testing Paxlovid against long COVID, including one late-stage study that may have results in about a year. 

“We already know that Paxlovid reduces the risk of developing long COVID, but it would be a game changer if it can improve long COVID symptoms as well,” said Surendra Barshikar, MD, an associate professor and medical director of the COVID Recover program at the University of Texas Southwestern Medical Center, Dallas. 

In other studies, researchers are looking at a wide variety of previously approved and experimental drugs and devices. For example, scientists in New York are testing the mood stabilizer lithium to treat brain fog and fatigue. And researchers in Illinois are investigating efgartigimod, a drug approved for the rare muscle-weakening autoimmune disorder myasthenia gravis, to see if it helps ease a long COVID complication known as POTS that can cause a sudden rapid heart rate and chronic fatigue. 

“The good news is that enrollment will proceed quickly, given the vast number of patients,” said Kristin Englund, MD, director of the reCOVer Center of Excellence at the Cleveland Clinic. 

This is all encouraging because roughly one in five American adults who have acute COVID infections develop persistent symptoms of long COVID, also known as post–acute sequelae of SARS-CoV-2 (PASC). And many of these long COVID patients have complex, overlapping clusters of symptoms that make traditional treatment approaches largely ineffective against this new, formidable disease. 

But not every patient living with long COVID will qualify for trials or find it easy to take part even if they do. Patients should consider how severe their symptoms are, the potential risks of any experimental treatments, and the many challenges they may have with getting to and from clinical trial sites that are largely concentrated around major cities and might be far from home. 

While this holds true for any type of trial, it’s essential for long COVID patients, who may have fatigue, muscle weakness, and other symptoms that make distance an impossible factor to ignore, said Aaron Friedberg, MD, clinical colead of the post–COVID-19 recovery program at the Ohio State University Wexner Medical Center, Columbus. 

“I think it is a personal decision, since the fatigue and pain that patients with PASC can experience can make it very challenging to travel long distances,” Dr. Friedberg said. “I would recommend calling or messaging ahead to find out exactly what type of travel might be required because there may be steps that can be completed by email or video, which could make it easier to participate, and some trials may be entirely remote.”

Even when patients feel up to the travel, they still might not be a good fit for a clinical trial. Scientists often look for people who didn’t have pre-existing health problems before they got long COVID, Dr. Barshikar noted. Patients taking medications may also be unable to participate in drug trials, particularly for experimental treatments because of concerns about unknown side effects from drug interactions. 

When clinical trials do seem like a good option, patients may want to consider seeking treatment at an academic medical center that is already doing long COVID research, particularly if their symptoms are too complex or severe to manage only through their primary care provider, said Jonathan Whiteson, MD, who helped draft long COVID treatment guidelines for the American Academy of Physical Medicine and Rehabilitation. He also serves as codirector of the New York University Langone Health post–COVID care program.

Many health care professionals on the front lines treating long COVID patients are optimistic that the sheer number of trials and the vast number of patients taking part should ultimately produce some better treatment options than people have right now. It’s just not going to happen overnight. 

“I suspect that while we will see some new treatments coming in the next 1-2 years, it may be several years before targets can be identified and full trials conducted to see results,” Dr. Friedberg said. “Getting good data takes time.”

A version of this article first appeared on WebMD.com.